Immune Response

Antioxid Redox Signal. 2015 Sep 28. [Epub ahead of print]

Phototherapy-induced antitumor immunity: long-term tumor supression effects via photoinactivation of respiratory chain oxidase-triggered superoxide anion burst.  

Lu C1,2, Zhou F3, Wu S4,5,6, Liu L7, Xing D8.
Author information
1Guangzhou, China.
2MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; lucx@scnu.edu.cn.
3MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; zhouff@scnu.edu.cn.
4South China Normal UniversityGuang Zhou, China , 510631.
5China.
6MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; wushn@scnu.edu.cn.
7MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , No. 55 Zhongshan Avenue West, Tianhe District,Guangzhou , guangzhou, China , 510631 ; liulei@scnu.edu.cn.
8South China Normal University , No. 55 Zhongshan west road, Tianhe district , guangzhou, China , 510631 ; xingda@scnu.edu.cn.

Abstract
AIMS:
Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high-fluence low-power laser irradiation (HF-LPLI) results in oxidative damage that induces tumor cell apoptosis. In this study, we focused on the immunological effects of HF-LPLI phototherapy and explored its antitumor immune regulatory mechanism.
RESULTS:
We found not only that HF-LPLI treatment induced tumor cell apoptosis but also that HF-LPLI-treated apoptotic tumor cells activated macrophages. Due to mitochondrial superoxide anion burst after HF-LPLI treatment, tumor cells displayed a high level of phosphatidylserine oxidation, which mediated the recognition and uptake by macrophages with the subsequent secretion of cytokines and generation of cytotoxic T lymphocytes. In addition, in vivo results showed that HF-LPLI treatment caused leukocyte infiltration into the tumor and efficaciously inhibited tumor growth in an EMT6 tumor model. These phenomena were absent in the respiration-deficient EMT6 tumor model, implying that the HF-LPLI-elicited immunological effects were dependent on the mitochondrial superoxide anion burst.
INNOVATION:
Here, for the first time, we show that HF-LPLI mediates tumor-killing effects via targeting photoinactivation respiratory chain oxidase to trigger a superoxide anion burst, leading to a high level of oxidatively modified moieties, which contributes to the phenotypic changes in macrophages and mediates the antitumor immune response.
CONCLUSION:
Our results suggest that HF-LPLI may be an effective cancer treatment modality that both eradicates the treated primary tumors and induces an antitumor immune response via photoinactivation of respiratory chain oxidase to trigger superoxide anion burst.
J Drugs Dermatol.  2014 May 1;13(5):564-8.

Update on the immunological mechanism of action behind phototherapy.

Tartar D, Bhutani T, Huynh M, Berger T, Koo J.

Abstract

Phototherapy is often used to treat inflammatory skin conditions such as psoriasis and eczema. Much progress has recently been made in understanding the mechanisms underlying the local, cutaneous immune effects induced by phototherapy. Unlike many immunosuppressive drugs used in the management of inflammatory skin disease, phototherapy not only targets effector immune cells but also appears to up-regulate regulatory T cells (Tregs). Additionally, phototherapy reverses epidermal barrier abnormalities common in these diseases, allowing for restoration of cutaneous homeostasis.<BR /><BR /> <EM>J Drugs Dermatol.</EM> 2014;13(5):564-568.

Vopr Kurortol Fizioter Lech.  2010 Sep-Oct;(5):30-3.

Analysis of parameters of reproductive tract mucosal immunity in women with chlamydial infection before and after local magnetolaserotherapy.

[Article in Russian]

Gizinger OA, Dolgushin II, Letiaeva OI.

Abstract

The objective of the present study was to evaluate the influence of combined treatment with low-intensity laser radiation and magnetic field on neutrophil function in women presenting with Chlamydial infection. Dysfunction of neutrophil granulocytes in these patients was manifest in the first place as the decreased number of phagocytes and the low rate of phagocytosis. It was shown that the concentration of active oxygen species in neutrophils in the patients with Chlamydial infection was significantly smaller than in healthy women. The concurrent application of low-intensity laser radiation and a magnetic field not only stimulated phagocytosis but also increased intracellular production of active oxygen species especially under in vitro conditions. It is concluded that combined treatment with low-intensity laser radiation and magnetic field has beneficial effect on the parameters of mucosal immunity in the reproductive tract of women with Chlamydial infection.

J Photochem Photobiol B. 2009 Dec 2;97(3):145-51. Epub 2009 Sep 11.

Effect of phototherapy with low intensity laser on local and systemic immunomodulation following focal brain damage in rat.

Moreira MS, Velasco IT, Ferreira LS, Ariga SK, Barbeiro DF, Meneguzzo DT, Abatepaulo F, Marques MM.LIM-51, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over therapeutic management for these patients. The objective of this study was to analyze the effect of phototherapy with low intensity lasers on local and systemic immunomodulation following cryogenic brain injury. Laser phototherapy was applied (or not-controls) immediately after cryogenic brain injury performed in 51 adult male Wistar rats. The animals were irradiated twice (3 h interval), with continuous diode laser (gallium-aluminum-arsenide (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP), 660 nm) in two points and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). The experimental groups were: Control (non-irradiated), RL3 (visible red laser/ 3 J/cm(2)), RL5 (visible red laser/5 J/cm(2)), IRL3 (infrared laser/3 J/cm(2)), IRL5 (infrared laser/5 J/cm(2)). The production of interleukin-1IL-1beta (IL-1beta), interleukin6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme immunoassay technique (ELISA) test in brain and blood samples. The IL-1beta concentration in brain of the control group was significantly reduced in 24 h (p<0.01). This reduction was also observed in the RL5 and IRL3 groups. The TNF-alpha and IL-6 concentrations increased significantly (p<0.01 and p<0.05, respectively) in the blood of all groups, except by the IRL3 group. The IL-6 levels in RL3 group were significantly smaller than in control group in both experimental times. IL-10 concentration was maintained stable in all groups in brain and blood. Under the conditions of this study, it is possible to conclude that the laser phototherapy can affect TNF-alpha, IL-1beta and IL-6 levels in the brain and in circulation in the first 24 h following cryogenic brain injury.

J Cell Mol Med. 2009 Sep 1. [Epub ahead of print]

Low Level Laser Irradiation Precondition to Create Friendly Milieu of Infarcted Myocardium and Enhance Early Survival of Transplanted Bone Marrow Cells.

 

Zhang H, Hou JF, Shen Y, Wang W, Wei YJ, Hu S.

Department of Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

We hypothesized that low-level laser irradiation (LLLI) precondition prior to cell transplantation might remodel the hostile milieu of infarcted myocardium and subsequently enhance early survival and therapeutic potential of implanted bone-marrow mesenchymal stem cells (BMSCs). Therefore, in this study we wanted to address: (1) whether LLLI pretreatment change the local cardiac micro-environment after MI; and (2) whether the LLLI preconditions enhance early cell survival and thus improve therapeutic angiogenesis and heart function. Myocardial infarction was induced by left anterior descending artery ligation in female rats. A 635 nm, 5 mW diode laser was performed with energy density of 0.96 J/cm(2) for 150 seconds for the purpose of myocardial precondition. Three weeks later, qualified rats were randomly received with LLLI precondition (n=26) or without LLLI precondition (n=27) for LLLI precondition study. Rats received thoracotomy without coronary ligation were served as sham group (n=24). For the following cell survival study, rats were randomly received serum-free culture media injection (n=8), LLLI precondition and culture media injection (n=8), 2 millions male BMSCs transplantation without LLLI pretreatment (n=26) and 2 millions male BMSCs transplantation with LLLI precondition (n=25). Vascular endothelial growth factor (VEGF), glucose-regulated protein 78 (GRP78), superoxide dismutase (SOD) and malondialdehyde (MDA) in the infarcted myocardium were evaluated by Western blotting, real-time polymerase chain reaction (real-time PCR) and colorimetry, respectively, at 1 hour, 1 day and 1 week after laser irradiation. Cell survival was assayed with quantitative real-time PCR to identify Y chromosome gene and apoptosis was assayed with TUNEL staining. Capillary density, myogenic differentiation and left ventricular function were tested by immunohistochemistry and echocardiography, respectively, at 1 week. After LLLI precondition, increased VEGF and GRP78 expression, as well as the enhanced SOD activity and inhibited MDA production, was observed. Compared with BMSCs transplantation and culture media injection group, although there was no difference in the improved heart function and myogenic differentiation, LLLI precondition significantly enhanced early cell survival rate by 2-fold, decreased the apoptotic percentage of implanted BMSCs in infarcted myocardium and thus increased the number of newly formed capillaries. Taking together, LLLI precondition could be a novel non-invasive approach for intraoperative cell transplantation to enhance cell early survival and therapeutic potential.

Anesth Analg. 2008 Sep;107(3):1058-63.

 

Pre-Irradiation of blood by gallium aluminum arsenide (830 nm) enhances peripheral endogenous opioid analgesia in rats.

 

Hagiwara S, Iwasaka H, Hasegawa A, Noguchi T.

Department of Brain and Nerve Science, Anesthesiology, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi-Yufu City-Oita 879-5593, Japan. saku@med.oita-u.ac.jp

BACKGROUND: Low-level laser therapy (LLLT) has been reported to relieve pain, free of side effects. However, the mechanisms underlying LLLT are not well understood. Recent studies have also demonstrated that opioid-containing immune cells migrate to inflamed sites and release beta-endorphins to inhibit pain as a mode of peripheral endogenous opioid analgesia. We investigated whether pre-irradiation of blood by LLLT enhances peripheral endogenous opioid analgesia. METHODS: The effect of LLLT pretreatment of blood on peripheral endogenous opioid analgesia was evaluated in a rat model of inflammation. Additionally, the effect of LLLT on opioid production was also investigated in vitro in rat blood cells. The expression of the beta-endorphin precursors, proopiomelanocortin and corticotrophin releasing factor, were investigated by reverse transcription polymerase chain reaction. RESULTS: LLLT pretreatment produced an analgesic effect in inflamed peripheral tissue, which was transiently antagonized by naloxone. Correspondingly, beta-endorphin precursor mRNA expression increased with LLLT, both in vivo and in vitro. CONCLUSION: These findings suggest that that LLLT pretreatment of blood induces analgesia in rats by enhancing peripheral endogenous opioid production, in addition to previously reported mechanisms.

Photomed Laser Surg. 2009 Apr;27(2):303-7.

Low-level laser therapy increases transforming growth factor-beta2 expression and induces apoptosis of epithelial cells during the tissue repair process.

Rocha Júnior AM, Vieira BJ, de Andrade LC, Aarestrup FM.

Universidade Federal de Juiz de Fora-MG, Laboratory of Immunopathology and Experimental Pathology, Juiz de Fora, Minas Gerais, Brazil.

BACKGROUND DATA: Low-level laser therapy (LLLT) has been reported to modulate the healing of wounds by inducing an increase in mitotic activity, fibroblast number, synthesis of collagen, and neovascularization. Objective: In the present study we evaluated the effect of LLLT on expression of TGF-beta(2), an immunosuppressive cytokine, at the site of tissue repair, using an experimental rat model to study cutaneous wound healing. In addition, we also investigated the presence of apoptotic cells in epithelial and connective tissue. MATERIALS AND METHODS: Thirty male Wistar rats were divided into two groups: group 1, which was subjected to surgical skin wounds only (n = 15), and group 2, which was subjected to surgical skin wounds followed by LLLT (n = 15). In group 2, the LLLT was given with these parameters: 15 mW of power, a dose of 3.8 J/cm(2), for 15 sec for three applications. At 10 d post-surgery and laser application the animals were sacrificed with an overdose of anesthetic and tissue samples from the wounds were submitted to immunohistochemistry and in-situ detection of apoptosis. RESULTS: Most of the inflammatory cells and fibroblasts were TGF-beta(2)-positive, and many apoptotic epithelial cells and fibroblasts were seen in the tissue samples from the LLLT-treated animals. However, a few apoptotic epithelial cells and fibroblasts were also seen in the samples obtained from control animals. CONCLUSION: Our results indicate that LLLT may be an important inducer of apoptosis during the process of tissue repair. In addition, we demonstrated that LLTT has an immunomodulatory effect on TGF-beta(2) expression at sites of wound healing.

Lasers Med Sci. 2008 Jul;23(3):331-5. Epub 2007 Sep 5.

Effects of low-level He-Ne laser irradiation on the gene expression of IL-1beta, TNF-alpha, IFN-gamma, TGF-beta, bFGF, and PDGF in rat’s gingiva.

Safavi SM, Kazemi B, Esmaeili M, Fallah A, Modarresi A, Mir M.

Center for Dental Research, Shaheed Beheshti University of Medical Sciences, Evin, Tehran 19834, Iran. safavismr@icdr.ac.ir

Biostimulatory effects of laser irradiation on cell proliferation and wound healing has been reported. However, little is known about the molecular basis of the mechanism. Interleukin 1beta (IL-1beta), tumor necrotic factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) play an important role in inflammation, while platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and blood-derived fibroblast growth factor (bFGF) are the most important growth factors of periodontal tissues. The aim of this study was to investigate the effect of low-level He-Ne laser on the gene expression of these mediators in rats’ gingiva and mucosal tissues. Twenty male Wistar rats were randomly assigned into four groups (A(24), A(48), B(24), B(48)) in which A(24) and A(48) were cases and B(24), B(48) were controls. An incision was made on gingiva and mucosa of the labial surface of the rats’ mandibular incisors. Group A(24) was irradiated twice with 24 hours interval, while the inflamed tissues of group A(48) was irradiated three times with continuous He-Ne laser (632.8 nm) at a dose of 7.5 J/cm2 for 300 s. An energy of 5.1 J was given to the 68 mm(2) irradiation zone. Rats were killed 30 min after the last irradiation of case and control groups, then excisional biopsy was performed. Gene expression of the cytokines was measured using reverse transcriptase-polymerase chain reaction (RT-PCR) technique. Results were analyzed with Kruskal-Wallis and Mann-Whitney U tests. The gene expression of IL-1beta and IFN-gamma was significantly inhibited in the test groups (P < 0.05), while the gene expression of PDGF and TGF-beta were significantly increased (P < 0.05). The case and control groups did not have a significant difference in the gene expression of TNF-alpha and bFGF (P > 0.05). These findings suggest that low-level He-Ne laser irradiation decreases the amount of inflammation and accelerates the wound healing process by changing the expression of genes responsible for the production of inflammatory cytokines.

J Physiol Pharmacol. 2007 Nov;58 Suppl 5(Pt 2):729-37

The influence of low-power helium-neon laser irradiation on function of selected peripheral blood cells.

Wasik M, Gorska E, Modzelewska M, Nowicki K, Jakubczak B, Demkow U.

Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland. MariaWasik@aster.pladiation

The effects of low-level laser light irradiation are debatable and the mechanisms of its action are still unclear. This study was conducted to test the effects of low-level laser irradiation on human blood cells: erythrocytes, granulocytes, and lymphocytes. Whole blood obtained by phlebotomy was irradiated at 632.8 nm by using energy fluences 0.6 J/cm2. An analysis of blood gases revealed an increase in PO2 and SaO2 (P<0.001) in irradiated blood. No shifts in PCO2 and pH were recorded. Spontaneous synthesis of DNA in T and B blood lymphocytes decreased significantly after laser irradiation (P<0.02 and P<0.04, respectively). Phytohemagglutinin (PHA)-induced proliferation of T cells and SAC proliferation of B cells, expressed as a stimulation index, were statistically higher in the samples of irradiated than in non-irradiated blood (P<0.01). Chemiluminescence of fMLP-stimulated granulocytes from irradiated blood increased in comparison with non-irradiated samples (P<0.001). No changes of spontaneous and stimulated chemiluminescence kinetics in irradiated samples were observed. These results reveal the influence of photodynamic reactions on the ability of blood to transport oxygen and on immunomodulatory effects on leukocytes.

Bull Exp Biol Med. 2007 Aug;144(2):238-40.

Effect of laser radiation on production of reactive oxygen species in the blood of patients with chronic obstructive pulmonary disease.

 

Farkhutdinov UR, Farkhutdinov ShU.

Department of Pulmonology, Clinical Hospital No. 21, Ufa.

The effect of laser radiation on generation of reactive oxygen species in the whole blood from patients with chronic obstructive pulmonary disease was studied by in vitro recording of luminol-dependent chemiluminescence. Laser irradiation of the blood from patients with increased production of reactive oxygen species decreased the microbicidal potential of cells. In patients with low generation of reactive oxygen species and normal potential of cells, laser exposure increased production of O2 metabolites. Laser radiation had little effect on chemiluminescence of the blood in patients with low generation of reactive oxygen species and decreased functional activity of cells.

Photodermatol Photoimmunol Photomed. 2006 Feb;22(1):33-8.

Effects of low-power laser radiation on mice immunity.

Novoselova EG, Glushkova OV, Cherenkov DA, Chudnovsky VM, Fesenko EE.

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino Scientific Centre, Moscow Region, Russia. elenanov@icb.psn.ru

Abstract

BACKGROUND/PURPOSE: Because of large interest in biological effects of laser radiation used in laser therapy, the effect of extremely low-level red laser light intensity on the immune cell activity has been studied in the animal model with well-characterized macrophage and T cell populations as responder cells producing cytokines, protective proteins, active oxygen, and nitric compounds. To study of the possible side effects of laser immunotherapy we monitored the productions of cytokines, nitric oxide (NO), and heat shock protein 70 (Hsp70) in mice subjected to a periodic laser exposure for 1 month. METHODS: Helium-neon laser radiation with the power of 0.2 mW/cm2 and wavelength of 632.8 nm was applied on two different mouse skin surfaces, i.e. a thymus projection area or a hind limb. Healthy NMRI male mice were irradiated repeatedly with laser light for 1 min with 48-h intervals for 30 days. The animals were divided into three groups of 25 mice. The first and the second groups were exposed to laser light, on the thymus and hind limb area, respectively. The third, sham-irradiated group served as a control. Early and prolonged effects of laser radiation on the levels of NO (by Griess assay), Hsp70 (by Western blot assay), tumor necrosis factors (TNF-alpha and TNF-beta) (by cytotoxic assay using L929 cells as targets), and interleukin-2 (IL-2) (by ELISA assay) were determined. RESULTS: The dynamics of immune responses to low-power laser light intensity was shown to be dependent on two factors, i.e. the cumulative dose and the localization of the irradiated surface. Besides, various populations of cells demonstrated different sensitivity to laser radiation, with T cells being more responsive among examined populations of the cells. Low intensity laser light induced an immune cell activity when the exposure duration did not exceed 10 days, while a more prolonged period of treatment generated more severe changes in the immune system, up to immunosuppression. The treatment of the thymus zone resulted in more pronounced changes in the cytokine production as well as in NO and Hsp70 synthesis. CONCLUSION: Low-power laser irradiation showed more effective immunomodulatory effects when applied on the thymus projection area. The rise in IL-2 and Hsp70 production related to a short-term effect of laser application may be reversed after repeating laser treatment. We suggest that for the support of immune system stability, the prolonged laser therapy should be accompanied by supplementary methods.

Biofizika. 2006 May-Jun;51(3):509-18.

Effect of low-intensity laser radiation (632.8 nm) on immune cells isolated from mice

[Article in Russian]

Novoselova EG, Cherenkov DA, Glushkova OV, Novoselova TV, Chudnovski? VM, Iusupov VI, Fesenko EE.

Abstract

The effect of in vitro exposure to low-power laser light with a power density of 0.2 mW/cm2 and a wavelength of 632.8 nm induced by helium-neon laser on the functional activity of macrophages and splenic lymphocytes was studied. If the exposure period did not exceed 60 sec, the stimulation in interleukin-2 (IL-2) and nitric oxide (NO) production, as well as an increase in the activity of natural killer cells were observed. The increase of irradiation dose by prolongation of the exposure duration up to 180 s induced a significant decrease in NO production and natural killer cell activity, but IL-2 production was not different from the control level. A remarkable decrease in interferon-gamma (IFN-gamma) production was observed following laser light exposure of cells for 60 or 180 s, whereas under lower doses (exposure for 5 or 30 sec) IFN-gamma production increased. Irradiation of isolated macrophages induced a significant stimulation of cellular tumor necrosis factor-alpha (TNF- alpha) production at all dboes used, and, what is more important, an enhancement in both TNF-a phaand interleukin-6 (IL-6) production was revealed as early as after a 5-s exposure. In this case, more prolonged exposure periods, 60 and 180 s, either did not induce changes in IL-6 production (in macrophages) or decreased IL-6 production (in lymphocytes). Thus, upon in vitro exposure of cells to extremely low-power laser light, a basic tendency was observed: short-term irradiation predominantly induced stimulation in secretory activity of cells, whereas prolongation of exposure mainly induced immunosuppression. The only exception to the rule was a change in interleukin-3 (IL-3) production, which decreased after short-time exposure, but, on the opposite, increased when the cells were exposed for 180 s. In addition, a high sensitivity to extremely low-power laser light was supported by expression of the inducible heat shock protein, Hsp70, the effect being observed at all doses used, including the exposure for 5 s. At the same time, expression of another heat shock protein, Hsp90, was somewhat reduced after irradiation of cells with laser light.

Photomed Laser Surg. 2005 Dec;23(6):571-4.

Helium-neon and nitrogen laser irradiation accelerates the phagocytic activity of human monocytes.

Hemvani N, Chitnis DS, Bhagwanani NS.

Department of Microbiology and Immunology, Choithram Hospital & Research Centre, Indore, India.

OBJECTIVE: Intracellular survival of mycobacteria within monocytes is a crucial stage in the pathogenesis of tuberculosis. The aim was to check intracellular survival of Mycobacterium fortuitum within the human monocytes exposed to He-Ne and nitrogen laser irradiation. BACKGROUND DATA: Tuberculosis remains one of the most important infectious diseases for developing countries. Low-level laser therapy (LLLT) has been tried to treat tubercular cavitory lung disease with encouraging results. The in vitro photobiological effect of low level laser radiation on the intracellular mycobacteria needs to be evaluated before we could go for large clinical trials. METHODS: The aliquots of human monocytes from peripheral blood of healthy volunteers and tuberculosis cases were exposed to He-Ne or nitrogen laser beam. The non-irradiated monocytes from the same source served as controls. The monocytes were then challenged with M. fortuitum, and surviving mycobacteria within monocytes were subjected to viable counts. RESULTS: Enhanced killing of mycobacterial cells was seen among monocytes exposed to He-Ne and nitrogen laser irradiation. CONCLUSIONS: He-Ne and nitrogen laser irradiation activates the monocytes to increase intracellular killing of mycobacteria.

Lasers Surg Med. 2008 Jul;40(5):371-8.

Irradiation with 780 nm diode laser attenuates inflammatory cytokines but upregulates nitric oxide in lipopolysaccharide-stimulated macrophages: implications for the prevention of aneurysm progression.

Gavish L, Perez LS, Reissman P, Gertz SD.

Department of Anatomy and Cell Biology, The Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel. lilachg@ekmd.huji.ac.il

BACKGROUND AND OBJECTIVES: Low level laser irradiation (LLLI) has been shown to reduce inflammation in a variety of clinical situations. We have shown that LLLI (780 nm) increases aortic smooth muscle cell proliferation and matrix protein secretion and modulates activity and expression of matrix metalloproteinases. Inflammation is a major component of arteriosclerotic diseases including aneurysm. Macrophage recruitment and secretion of pro-inflammatory cytokines and the vasodilator, nitric oxide (NO), are central to most immune responses in the arterial wall. The present study was designed to determine the effect of LLLI on cytokine gene expression and secretion as well as gene expression of inducible nitric oxide synthase (iNOS) and NO production in lipopolysaccharide (LPS)-stimulated macrophages. STUDY DESIGN/MATERIALS AND METHODS: Murine monocyte/macrophages (RAW 264.7) were irradiated with a 780 nm diode laser (2 mW/cm(2), 2.2 J/cm(2)) during stimulation with LPS (0, 0.1, and 1 microg/ml). Gene expression of chemokines, cytokines, and iNOS were assessed by RT-PCR. Secretion of interleukin (IL)-1beta and monocyte chemotactic protein (MCP)-1 and NO were assessed by ELISA and the Griess reaction, respectively. RESULTS: LLLI reduced gene expression of MCP-1, IL-1alpha, IL-10 (P<0.01), IL-1beta, and IL-6 (P<0.05) when cells were stimulated by 1 microg/ml LPS. LLLI reduced LPS-induced secretion of MCP-1 over non-irradiated cells by 17+/-5% and 13+/-5% at 12 hours (0.1 and 1 microg/ml LPS; P<0.01 and P=0.05, respectively), and reduced IL-1beta by 22+/-5% and 25+/-9% at 24 hours (0.1 and 1 microg/ml LPS, P=0.01 and P=0.06, respectively). However, LLLI increased NO secretion after 12 hours (LLLI vs. Control: without LPS, 1.72+/-0.37 vs. 0.95+/-0.4 microM, P<0.05; 0.1 microg/ml LPS, 7.46+/-1.62 vs. 4.44+/-1.73 microM, P=0.06; 1 microg/ml LPS, 10.91+/-3.53 vs. 6.88+/-1.52 microM, P<0.05). CONCLUSIONS: These properties of LLLI, with its effects on smooth muscle cells reported previously, may be of profound therapeutic relevance for arterial diseases such as aneurysm where inflammatory processes and weakening of the matrix structure of the arterial wall are major pathologic components.

Gen Dent. 2008 Nov-Dec;56(7):629-34.

Low level lasers in dentistry.

Ross G, Ross A.

Laser Light Canada.

Low level laser therapy (LLLT) uses light energy, in the form of adenosine triphosphate (ATP), to elicit biological responses in the body. The increased cellular energy and changes in the cell membrane permeability result in pain relief, wound healing, muscle relaxation, immune system modulation, and nerve regeneration. This article investigates the clinical effects of LLLT and explains how it can be applied in the dental field.

Biofizika. 2007 Jan-Feb;52(1):137-40.

Protective effect of low-power laser radiation in acute toxic stress

[Article in Russian]

Novoselova EG, Glushkova OV, Khrenov MO, Chernenkov DA, Lunin SM, Novoselova TV, Chudnovski? VM, Iusupov VI, Fesenko EE.

The effect of preliminary short-term irradiation with He-Ne laser light (632.8 nm, 0.2 mW/cm2) of the thymus zone projection of male NMRI mice subjected to acute toxic stress on the responses of immune cells was studied. Stress was modeled by lipopolysaccharide injection, 250 mg/100 g of body weight, which induced a significant increase in the production of several macrophage cytokines, IL-1alpha, IL-1beta, IL-6, IL-10 and TNF-alpha. A single irradiation with laser light did not provoke considerable variations in NO production in cells but induced an enhancement in the production of heat shock proteins Hsp25, Hsp70, and Hsp90. Nevertheless, when irradiation with red laser light was applied prior to toxic stress, considerable normalization of production of nearly all cytokines studied and nitric oxide was observed. Moreover, the normalization of production of heat shock proteins has been shown in these conditions. Thus, preliminary exposure of a small area of animal skin surface provoked a significant lowering in the toxic effect of

J Physiol Pharmacol. 2007 Nov;58 Suppl 5(Pt 2):729-37.

The influence of low-power helium-neon laser irradiation on function of selected peripheral blood cells.

Wasik M, Gorska E, Modzelewska M, Nowicki K, Jakubczak B, Demkow U.

Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Warsaw Medical University, Warsaw, Poland. MariaWasik@aster.pladiation

The effects of low-level laser light irradiation are debatable and the mechanisms of its action are still unclear. This study was conducted to test the effects of low-level laser irradiation on human blood cells: erythrocytes, granulocytes, and lymphocytes. Whole blood obtained by phlebotomy was irradiated at 632.8 nm by using energy fluences 0.6 J/cm2. An analysis of blood gases revealed an increase in PO2 and SaO2 (P<0.001) in irradiated blood. No shifts in PCO2 and pH were recorded. Spontaneous synthesis of DNA in T and B blood lymphocytes decreased significantly after laser irradiation (P<0.02 and P<0.04, respectively). Phytohemagglutinin (PHA)-induced proliferation of T cells and SAC proliferation of B cells, expressed as a stimulation index, were statistically higher in the samples of irradiated than in non-irradiated blood (P<0.01). Chemiluminescence of fMLP-stimulated granulocytes from irradiated blood increased in comparison with non-irradiated samples (P<0.001). No changes of spontaneous and stimulated chemiluminescence kinetics in irradiated samples were observed. These results reveal the influence of photodynamic reactions on the ability of blood to transport oxygen and on immunomodulatory effects on leukocytes.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007 Jun;103(6):764-73. Epub 2006 Nov 7.

A preliminary study of healing of diode laser versus scalpel incisions in rat oral tissue: a comparison of clinical, histological, and immunohistochemical results.

D’Arcangelo C, Di Nardo Di Maio F, Prosperi GD, Conte E, Baldi M, Caputi S.

University G. D’Annunzio, Faculty of Medicine, Department of Oral Science, Unit of Restorative Dentistry, Chieti, Italy.

OBJECTIVE: The aim of this preliminary study was to compare wound healing of rat oral tissues after surgical procedure with diode laser or scalpel. Healing was evaluated histologically, immunohistochemically, and by measurement of 2 nitric oxide synthase isoforms (eNOS and iNOS) as intracellular messenger molecules with important immune functions. The instruments were also evaluated for performance and ease of use. STUDY DESIGN: Twenty-four standardized incisions were performed in the hard palate of 12 male Wistar rats. Each rat received 2 incisions on the opposite sides of the palate by using a steel scalpel (control group) and a diode laser (808 nm) at a power output of 4 W and 6 W (test group). Histological and immunohistochemical analyses were performed on tissue samples after 7 and 14 days. The expression of eNOS and iNOS was confirmed by RT-PCR (reverse transcriptase-polymerase chain reaction) and Western blot analysis. RESULTS: Scalpel repair was found to be equivalent to or better than laser repair at the intervals measured. Histological analysis showed that incision wound repair after laser surgical procedure was related to parameters and beam characteristics. Diode laser at a power output of 6 W showed the worst results of tissue repair, especially after 7 days. On the contrary, the extent of epithelial damage lateral to the wound edge and the extent of collagen denaturation were near equal with scalpel incision and laser irradiation at 4 W after 14 days. Biochemical analysis of RT-PCR and Western blots also confirmed histological results with a greater concentration of eNOS and iNOS after 7 days of laser surgical procedure. CONCLUSIONS: Clinical and histological findings change over time for different treatments. Diode laser tends to produce more pronounced changes than conventional scalpel surgical procedure (due to tissue thermal damage), with corresponding greater inflammatory reaction and delay in tissue organization only at the initial stage. Thus, long-term histology is critical for predicting treatment results. The clinical use of low-level diode laser for tissue welding of oral mucosa should be investigated further, since it appears to be a good alternative to scalpel incision and suture repair.

Photomed Laser Surg. 2007 Apr;25(2):112-7.

Effect of low-level laser therapy on hemorrhagic lesions induced by immune complex in rat lungs.

Aimbire F, Lopes-Martins RA, Albertini R, Pacheco MT, Castro-Faria-Neto HC, Martins PS, Bjordal JM.

Laboratory of Animal Experimentation, Research and Development Institute (IP&D), Vale do Paraíba University (UNIVAP), São José dos Campos, Brazil.

OBJECTIVE: The aim of this study was to investigate if low-level laser therapy (LLLT) can modulate formation of hemorrhagic lesions induced by immune complex. BACKGROUND DATA: There is a lack of information on LLLT effects in hemorrhagic injuries of high perfusion organs, and the relative efficacy of LLLT compared to anti-inflammatory drugs. METHODS: A controlled animal study was undertaken with 49 male Wistar rats randomly divided into seven groups. Bovine serum albumin (BSA) i.v. was injected through the trachea to induce an immune complex lung injury. The study compared the effect of irradiation by a 650-nm Ga-Al-As laser with LLLT doses of 2.6 Joules/cm(2) to celecoxib, dexamethasone, and control groups for hemorrhagic index (HI) and myeloperoxide activity (MPO) at 24 h after injury. RESULTS: The HI for the control group was 4.0 (95% CI, 3.7-4.3). Celecoxib, LLLT, and dexamethasone all induced significantly (p < 0.01) lower HI than control animals at 2.5 (95% CI, 1.9-3.1), 1.8 (95% CI, 1.2-2.4), and 1.5 (95% CI, 0.9-2.1), respectively, for all comparisons to control. Dexamethasone, but not celecoxib, induced a slightly, but significantly lower HI than LLLT (p = 0.04). MPO activity was significantly decreased in groups receiving celecoxib at 0.87 (95% CI, 0.63-1.11), dexamethasone at 0.50 (95% CI, 0.24-0.76), and LLLT at 0.7 (95% CI, 0.44-0.96) when compared to the control group, at 1.6 (95% CI, 1.34-1.96; p < 0.01), but there were no significant differences between any of the active treatments. CONCLUSION: LLLT at a dose of 2.6 Joules/cm(2) induces a reduction of HI levels and MPO activity in hemorrhagic injury that is not significantly different from celecoxib. Dexamethasone is slightly more effective than LLLT in reducing HI, but not MPO activity.

Biofizika. 2007 Sep-Oct;52(5):888-92.

[The role of transcription factors in the response of mouse lymphocytes to low-level electromagnetic and laser radiations]

[Article in Russian]

Khrenov MO, Cherenkov DA, Glushkova OV, Novoselova TV, Lunin SM, Parfeniuk SB, Lysenko EA, Novoselova EG, Fesenko EE.

The effects of low-intensity laser radiation (LILR, 632.8 nm, 0.2 mW/cm2) and low-intensity electromagnetic waves (LIEW, 8.15 – 18 GHz, 1 MW/cm2) on the production of transcription factors in lymphocytes from NMRI male mice were examined. The total level of NF-KB and its phosphorylated metabolite Phospho-NF-kappaB, as well as the regulatory protein IkappaB-alpha were determined in spleen lymphocytes subjected to laser or microwave radiations. The proteins were determined by immunoblotting. Laser light induced a lowering in the level of NF-kappaB and IkappaB-alpha. By contrast, irradiation with electromagnetic waves resulted in a significant increase in the amount of NF-kappaB and IkappaB-alpha. The phosphorylated form of NF-kappaB did not noticeably change under either of the two kinds of radiation. The results showed that electromagnetic waves activate the production of both NF-kappaB and the regulatory protein IkappaB-alpha and these data confirm the stress character of the response of spleen lymphocytes to low-level microwaves of the centimeter range.

Zh Mikrobiol Epidemiol Immunobiol. 2006 Jul-Aug;(4):105-9.

Immunological and microbiological aspects of low intensity laser effect on the factors of local immunity of the reproductive tract in women with chlamydia infection

 

[Article in Russian]

Dolgushin II, Gizinger OA, Telesheva LF.

Assessment of immunological and microbiological efficacy of Chlamydia cervicitis management was made by a complex method with a low intensity laser. The total number of leukocytes, percentage of viable cells and the number of neutrophils were detected in cervical secrets. Functional status of neutrophils was studied by a content of lysosomes on the ground of spontaneous and induced by latex HCT-reducing capacity, phagocytic activity. A system of cytokines was studied by interleukine level (IL-1 alpha, IL-1 beta, TNF-alpha, IL-8) and IFN-gamma content in cervical mucus. Positive clinical effect of the local use of the low intensity laser for Chlamydia cervicitis treatment was accompanied by positive changes in immunological indices of cervical secret, normal concentration of cytokines in cervical secret, restoration of the number and functions of neutrophils. Local use of the low intensity laser contributed to decreased number of opportunistic pathogenic microorganisms and their associations, and restored local flora.

J Nippon Med Sch. 2006 Apr;73(2):75-81.

Light-emitting diode phototherapy at 630 +/- 3 nm increases local levels of skin-homing T-cells in human subjects.

Takezaki S, Omi T, Sato S, Kawana S.

Department of Dermatology, Nippon Medical School, Sendagi, Tokyo, Japan.

BACKGROUND AND AIMS: Red light phototherapy with laser sources has been used successfully for a number of indications. A new generation of quasimonochromatic 630 +/- 3 nm light-emitting diode (LED) systems has recently been yielding good results for the same indications, but no study has examined changes in visible red light irradiated skin at an immunological level. This study was thus designed to examine changes in skin-homing T-cell levels induced in normal human skin by visible red LED energy. SUBJECTS AND METHODS: Six adult male volunteers (35 approximately 48 years old) who satisfied all study criteria had the skin over the lateral aspect of the leg irradiated once per week for 8 weeks with a visible red (630 +/- 3 nm) LED-based system, with irradiance of 105 m/cm2, 15 minutes/session, and a radiant flux of 94 J/cm2. Skin biopsies were performed after the eighth treatment session, and cultures were prepared to assay the type and quantity of skin-homing T-cells using qualitative and quantitative polymerase chain reaction (PCR) techniques. Ultrastructural changes were also assessed with transmission electron microscopy. RESULTS: Transmission electron microscopy revealed mild fibroplastic changes in fibroblasts, with no acute inflammatory changes throughout the treatment session. Qualitative PCR showed the presence of both Th-1 and Th-2 T-cells, and quantitative PCR showed an increase in the numbers of both types of skin-homing T-cells, much more so for Th-2 than for Th-1. CONCLUSIONS: Visible red LED irradiation appears to activate the skin-homing immune system.

Br J Dermatol. 2005 Dec;153 Suppl 2:57-62.

Cutaneous immunological activation elicited by a low-fluence pulsed dye laser.

Omi T, Kawana S, Sato S, Takezaki S, Honda M, Igarashi T, Hankins RW, Bjerring P, Thestrup-Pedersen K.

Department of Dermatology, Queen’s Square Medical Centre, Yokohama, Japan. tomi@olive.ocn.ne.jp

BACKGROUND: Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes. MATERIALS AND METHODS: Eight healthy adult volunteers (mean age 56.3 years, range 25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction. RESULTS: Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects. CONCLUSION: The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.

Biofizika. 2006 May-Jun;51(3):509-18.

Effect of low-intensity laser radiation (632.8 nm) on immune cells isolated from mice

[Article in Russian]

  • Novoselova EG,
  • Cherenkov DA,
  • Glushkova OV,
  • Novoselova TV,
  • Chudnovskii VM,
  • Iusupov VI,
  • Fesenko EE.

The effect of in vitro exposure to low-power laser light with a power density of 0.2 mW/cm2 and a wavelength of 632.8 nm induced by helium-neon laser on the functional activity of macrophages and splenic lymphocytes was studied. If the exposure period did not exceed 60 sec, the stimulation in interleukin-2 (IL-2) and nitric oxide (NO) production, as well as an increase in the activity of natural killer cells were observed. The increase of irradiation dose by prolongation of the exposure duration up to 180 s induced a significant decrease in NO production and natural killer cell activity, but IL-2 production was not different from the control level. A remarkable decrease in interferon-gamma (IFN-gamma) production was observed following laser light exposure of cells for 60 or 180 s, whereas under lower doses (exposure for 5 or 30 sec) IFN-gamma production increased. Irradiation of isolated macrophages induced a significant stimulation of cellular tumor necrosis factor-alpha (TNF- alpha) production at all dboes used, and, what is more important, an enhancement in both TNF-a phaand interleukin-6 (IL-6) production was revealed as early as after a 5-s exposure. In this case, more prolonged exposure periods, 60 and 180 s, either did not induce changes in IL-6 production (in macrophages) or decreased IL-6 production (in lymphocytes). Thus, upon in vitro exposure of cells to extremely low-power laser light, a basic tendency was observed: short-term irradiation predominantly induced stimulation in secretory activity of cells, whereas prolongation of exposure mainly induced immunosuppression. The only exception to the rule was a change in interleukin-3 (IL-3) production, which decreased after short-time exposure, but, on the opposite, increased when the cells were exposed for 180 s. In addition, a high sensitivity to extremely low-power laser light was supported by expression of the inducible heat shock protein, Hsp70, the effect being observed at all doses used, including the exposure for 5 s. At the same time, expression of another heat shock protein, Hsp90, was somewhat reduced after irradiation of cells with laser light.

Photodermatol Photoimmunol Photomed. 2006 Feb;22(1):33-8.

Effects of low-power laser radiation on mice immunity.

Novoselova EG, Glushkova OV, Cherenkov DA, Chudnovsky VM, Fesenko EE.

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino Scientific Centre, Moscow Region, Russia. elenanov@icb.psn.ru

BACKGROUND/PURPOSE: Because of large interest in biological effects of laser radiation used in laser therapy, the effect of extremely low-level red laser light intensity on the immune cell activity has been studied in the animal model with well-characterized macrophage and T cell populations as responder cells producing cytokines, protective proteins, active oxygen, and nitric compounds. To study of the possible side effects of laser immunotherapy we monitored the productions of cytokines, nitric oxide (NO), and heat shock protein 70 (Hsp70) in mice subjected to a periodic laser exposure for 1 month. METHODS: Helium-neon laser radiation with the power of 0.2 mW/cm2 and wavelength of 632.8 nm was applied on two different mouse skin surfaces, i.e. a thymus projection area or a hind limb. Healthy NMRI male mice were irradiated repeatedly with laser light for 1 min with 48-h intervals for 30 days. The animals were divided into three groups of 25 mice. The first and the second groups were exposed to laser light, on the thymus and hind limb area, respectively. The third, sham-irradiated group served as a control. Early and prolonged effects of laser radiation on the levels of NO (by Griess assay), Hsp70 (by Western blot assay), tumor necrosis factors (TNF-alpha and TNF-beta) (by cytotoxic assay using L929 cells as targets), and interleukin-2 (IL-2) (by ELISA assay) were determined. RESULTS: The dynamics of immune responses to low-power laser light intensity was shown to be dependent on two factors, i.e. the cumulative dose and the localization of the irradiated surface. Besides, various populations of cells demonstrated different sensitivity to laser radiation, with T cells being more responsive among examined populations of the cells. Low intensity laser light induced an immune cell activity when the exposure duration did not exceed 10 days, while a more prolonged period of treatment generated more severe changes in the immune system, up to immunosuppression. The treatment of the thymus zone resulted in more pronounced changes in the cytokine production as well as in NO and Hsp70 synthesis. CONCLUSION: Low-power laser irradiation showed more effective immunomodulatory effects when applied on the thymus projection area. The rise in IL-2 and Hsp70 production related to a short-term effect of laser application may be reversed after repeating laser treatment. We suggest that for the support of immune system stability, the prolonged laser therapy should be accompanied by supplementary methods.

J Photochem Photobiol B. 2006 May 1;83(2):87-93. Epub 2006 Feb 7.

Effect of low-level helium-neon laser therapy on the healing of third-degree burns in rats.

 

Bayat M, Vasheghani MM, Razavi N.

Cell and Molecular Biology Research Center, Department of Anatomy, School of Medicine, Shaheed Beheshti University of Medical Sciences, P.O. Box 19395/4719, Tehran, Evin 1985717443, Iran. bayat_m@yahoo.com

This paper presents the results of a study on the effects of low-level helium-neon laser therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult male rats, having been subjected to third-degree burns, were randomly divided into four groups: two laser treated groups (n=20, each), one control group (n=19) and one nitrofurazone treated group (n=19). In the two laser treated groups, the burns were treated on a daily basis with LL He-Ne LT with an energy density of 1.2 and 2.4 J/cm(2), respectively. The response to treatment was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at day 15. Analysis of variance showed that the mean of blood vessel sections in the 1.2J/cm(2) laser group was significantly higher than those in the other groups and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group on day 16 was significantly lower than in the nitrofurazone treated group (P=0.025, P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa grew in more than 50% of samples obtained from control group, there were no S. aureus and P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is concluded that LL He-Ne LT induced the destruction of S. aureus and P. aeruginosa in third-degree burns of rats, yet at the same time our histological findings showed that LL He-Ne LT caused a significant increase in the mean of blood vessel sections on day 7 after third degree burns and a decrease in the mean of the depth of new epidermis on day 16 after the same burns in rats.

Photodermatol Photoimmunol Photomed. 2006 Feb;22(1):33-8.

Effects of low-power laser radiation on mice immunity.

Novoselova EG, Glushkova OV, Cherenkov DA, Chudnovsky VM, Fesenko EE.

Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino Scientific Centre, Moscow Region, Russia.

Background/purpose: Because of large interest in biological effects of laser radiation used in laser therapy, the effect of extremely low-level red laser light intensity on the immune cell activity has been studied in the animal model with well-characterized macrophage and T cell populations as responder cells producing cytokines, protective proteins, active oxygen, and nitric compounds. To study of the possible side effects of laser immunotherapy we monitored the productions of cytokines, nitric oxide (NO), and heat shock protein 70 (Hsp70) in mice subjected to a periodic laser exposure for 1 month. Methods: Helium-neon laser radiation with the power of 0.2 mW/cm(2) and wavelength of 632.8 nm was applied on two different mouse skin surfaces, i.e. a thymus projection area or a hind limb. Healthy NMRI male mice were irradiated repeatedly with laser light for 1 min with 48-h intervals for 30 days. The animals were divided into three groups of 25 mice. The first and the second groups were exposed to laser light, on the thymus and hind limb area, respectively. The third, sham-irradiated group served as a control. Early and prolonged effects of laser radiation on the levels of NO (by Griess assay), Hsp70 (by Western blot assay), tumor necrosis factors (TNF-alpha and TNF-beta) (by cytotoxic assay using L929 cells as targets), and interleukin-2 (IL-2) (by ELISA assay) were determined. Results: The dynamics of immune responses to low-power laser light intensity was shown to be dependent on two factors, i.e. the cumulative dose and the localization of the irradiated surface. Besides, various populations of cells demonstrated different sensitivity to laser radiation, with T cells being more responsive among examined populations of the cells. Low intensity laser light induced an immune cell activity when the exposure duration did not exceed 10 days, while a more prolonged period of treatment generated more severe changes in the immune system, up to immunosuppression. The treatment of the thymus zone resulted in more pronounced changes in the cytokine production as well as in NO and Hsp70 synthesis. Conclusion: Low-power laser irradiation showed more effective immunomodulatory effects when applied on the thymus projection area. The rise in IL-2 and Hsp70 production related to a short-term effect of laser application may be reversed after repeating laser treatment. We suggest that for the support of immune system stability, the prolonged laser therapy should be accompanied by supplementary methods.

Biofizika. 2006 Jan-Feb;51(1):123-35.

 

Effects of exposure of different skin areas to low-power laser light

 

[Article in Russian]

Glushkov OV, Novoselova EG, Cherenkov DA, Novoselova TV, Khrenov MO, Lunin SM, Chudnovski? VM, Iusupov VI, Fesenko EE.

The effect of helium-neon laser light of extremely low power of 0.2 mW/cm2 and wavelength 632.8 nm on the immune status of mice bearing solid tumors was studied. The evaluation of the status of tumor-bearing animals was provided by taking into account the number of immune cells, cytokine concentration (tumor necrosis factor, interleukin 2, production of nitric oxide, expression of heat shock proteins (Hsp70 and Hsp90), and activity of natural killers. The model of a solid tumor was formed by subcutaneous injection of Ehrlich carcinoma cells, and average life span of tumor-bearing mice achieved about 55 days. Different areas of the skin of tumor-bearing mice were subjected either to a single (1 min, dose 0.012 J/cm3) or repeated exposure to laser light (1 min, 48-h intervals, 30 days). Two different areas were irradiated: the thymus projection area or a hind limb with solid tumors. The results showed that chronic exposure of tumor-bearing mice in the thymus projection area, and especially, hind limb, reduced the resistance, which manifested itself in the acceleration of tumor growth and a tendency of mouse life span to decrease. On the contrary, a single exposure stimulated the antitumor immunity for several days after the exposure. The results show the expediency of further investigation of the immunomodulative effects of low-power laser light and the necessity of monitoring the immune system during laser therapy.

Photomed Laser Surg. 2005 Dec;23(6):571-4.

Helium-neon and nitrogen laser irradiation accelerates the phagocytic activity of human monocytes.

 

Hemvani N, Chitnis DS, Bhagwanani NS.

Department of Microbiology and Immunology, Choithram Hospital & Research Centre, Indore, India.

OBJECTIVE: Intracellular survival of mycobacteria within monocytes is a crucial stage in the pathogenesis of tuberculosis. The aim was to check intracellular survival of Mycobacterium fortuitum within the human monocytes exposed to He-Ne and nitrogen laser irradiation. BACKGROUND DATA: Tuberculosis remains one of the most important infectious diseases for developing countries. Low-level laser therapy (LLLT) has been tried to treat tubercular cavitory lung disease with encouraging results. The in vitro photobiological effect of low level laser radiation on the intracellular mycobacteria needs to be evaluated before we could go for large clinical trials. METHODS: The aliquots of human monocytes from peripheral blood of healthy volunteers and tuberculosis cases were exposed to He-Ne or nitrogen laser beam. The non-irradiated monocytes from the same source served as controls. The monocytes were then challenged with M. fortuitum, and surviving mycobacteria within monocytes were subjected to viable counts. RESULTS: Enhanced killing of mycobacterial cells was seen among monocytes exposed to He-Ne and nitrogen laser irradiation. CONCLUSIONS: He-Ne and nitrogen laser irradiation activates the monocytes to increase intracellular killing of mycobacteria.

Photodermatol Photoimmunol Photomed. 2003 Aug;19(4):203-12.

 

Immunomodulatory effects of low-intensity near-infrared laser irradiation on contact hypersensitivity reaction.

Kandolf-Sekulovic L, Kataranovski M, Pavlovic MD.

Department of Dermatology and Institute for Medical Research, Military Medical Academy, Belgrade, Serbia and Montenegro.

BACKGROUND/PURPOSE: Contact hypersensitivity (CHS) reaction is a useful model for studying the skin immune system and inflammatory reactions in the skin. In this study, an experimental model of CHS reaction was employed to assess immunomodulatory effects of near-infrared (near-IR) low-intensity laser (LIL) irradiation, which is used as adjuvant therapy in dermatology, physical medicine, rheumatology, etc., because of its declared anti-inflammatory, biostimulative and analgesic effects. METHODS: The effects of near-IR LIL irradiation (lambda=904 nm, irradiance 60 mW/cm2, fluence 3.6 J/cm2) on CHS reaction to 1-chloro-2,4-dinitrochlorobenzene (DNCB) in Albino Oxford rats were examined by irradiating experimental groups of animals before the induction phase of CHS reaction, while nonirradiated animals and animals that received vehicle instead of hapten served as controls. Ear-swelling assay, histopathological examination of H&E preparations of ear skin, computer-assisted image analysis of dermal infiltrate, ear skin organ culture with the determination of cutaneous production of tumour necrosis factor-alpha (by ELISA assay) and nitric oxide (by Griess’ assay) were used for measuring the effects of LIL in the elicitation phase of CHS reaction. Cellularity, dendritic cell content, flow cytometry and proliferation assays (spontaneous and in the presence of IL-2 and concanavalin A) of the draining lymph node cells (DLNC) were performed for the assessment of LIL irradiation effects in the induction phase. RESULTS: In the irradiated group of animals, ear swelling was significantly diminished compared to control animals (101+/-11.5% vs. 58+/-11.6%, P<0.01). This was accompanied by a highly significant decrease in the density of dermal infiltrate (22+/-0.81 vs. 14.2+/-1.75 cells per unit area, P<0.01) and a significant decrease in nitrite levels in the medium conditioned by organ-cultured ear skin (17.63+/-1.91 vs. 3.16+/-1.69 microM NaNO2; P<0.01), while TNF-alpha concentration was not changed. Cellularity and dendritic cell content in DLNC population, as well as the expression of TCR-alpha, CD4, CD8 and CD25, were not changed between irradiated and nonirradiated animals. Proliferation rates of DLNC cultured for 72 h were significantly lower in irradiated animals (17.3+/-4.1 vs. 13.9+/-0.9 x 103 c.p.m.; P<0.01). In cultures of DLNC with added rIL-2 or 0.5 microg/ml of concanavalin A, proliferation rates were also significantly decreased in irradiated animals (34.7+/-3.5 vs. 31.2+/-2. c.p.m. in IL-2-supplemented culture, P<0.01; 70.9+/-6.4 vs. 58.3+/-9.1 x 103 c.p.m. in concanavalin A-supplemented culture, P<0.01). However, this effect was overcome in the presence of the higher concentration of concanavalin A (2.5 microg/ml) (nonirradiated 38.7+/-3.1, irradiated 123.1+/-7.3 x 103 c.p.m., P<0.01). CONCLUSION: LIL irradiation showed a systemic immunomodulatory effect on CHS reaction to DNCB in rats. Decreased ear swelling observed in the elicitation phase was associated with diminished proliferative responses of the DLNC in the induction phase of CHS reaction. Further experimental work is needed to examine the possible mechanisms of these effects.

Lik Sprava. 2004 Mar;(2):30-5.

Effect of low intensity helium-neon laser and decimeter electromagnetic irradiation on functional indices of immune cells in patients with rheumatoid arthritis

[Article in Russian]

Petrov AV.

Clinical, laboratory, and immunoassay of 58 patients with rheumatoid arthritis, first and second degree of activity was carried out. Low-energy helium-neon laser exposure and decimeter electromagnetic radiation (DMEM) of peripheral blood was given along with the use of non-steroidal antiinflammatory drugs and methotrexate. Peculiarities of this magnetic-laser effect on proliferation response and apoptosis of mononuclear leucocytes in vitro and in vivo have been revealed. It was also established that the application of DMEM-therapy brought patients with RA in shorter period of time to clinical improvement evaluated by ACR criteria.

Eksp Klin Gastroenterol. 2004;(4):29-32, 108.

State of humoral immunity and phagocytic activity in neutrophils in patients with ulcer and effect of low-intensity laser therapy

[Article in Russian]

Burduli NM, Gutnova SK.

The aim of our investigation was to study the influence of low-intensity laser therapy at the immunologic parameters and Helicobacter pylori (HP) microbial contamination in patients with exacerbation of peptic and duodenal ulcer. 100 patients aged 18-65 were examined and divided into 2 groups. The experimental group (75 patients) underwent a complex drug and laser therapy of various therapeutic techniques. The control group (25 patients) underwent only drug therapy. The results of this study show the immunocorrective effect of different methods of low-intensity laser therapy in the exacerbation period and more essential decrease of HP microbial contamination in the experimental group.

Photomed Laser Surg. 2004 Dec;22(6):504-8.

Cell survival, DNA, and protein damage in B14 cells under low-intensity near-infrared (810 nm) laser irradiation.

Kujawa J, Zavodnik IB, Lapshina A, Labieniec M, Bryszewska M.

Department of Rehabilitation, Medical University of Lodz, Lodz, Poland. jkujawa@box43.gnet.pl

OBJECTIVE: The aim of this study was to reveal the possible cytotoxic and genotoxic effects of low-intensity (200 mW) near-infrared (810 nm) laser irradiation, using B14 cell line. BACKGROUND DATA: Laser therapy is widely used in biomedical treatment of many diseases, but the possible molecular mechanisms of laser actions remain unclear and the damaging effects of laser irradiation are still controversial. The side effects of laser therapy involve the generation of reactive oxygen and nitrogen species which in turn initiate lipid peroxidation, protein damage or DNA modification. METHODS: B14 cells and suspension of human erythrocyte membranes were irradiated with near-infrared (810 nm) therapy laser at different radiant exposures (3.75-15.0 J/cm(2)) and light power (fluency rate) 200 mW at 22 degrees C. Laser induced cellular oxidative damage was measured in terms of cell survival, DNA damage, measured using the method of single cell gel electrophoresis (Comet assay), protein damage measured as protein carbonyls formation. RESULTS: No substantial changes of cell survival under B14 cells irradiation at radiant exposures 3.75-11.25 J/cm(2) were observed. Similarly, neither considerable light-induced DNA damage or protein carbonyls accumulation was revealed. On the contrary, laser irradiation has led to decrease of cell protein carbonyl groups level in a dose-dependent manner. Additionally, using human red blood cell membranes as model membranes and biological oxidant HOCl we observed that laser irradiation resulted in a decrease of the level of membrane protein carbonyl groups accumulated under oxidative HOCl treatment. CONCLUSIONS: We can conclude that laser irradiation used (810 nm, 200 mW, 3.75-11.25 J/cm(2)) did not produce any considerable cytotoxic or genotoxic effects in B14 cells. Moreover, laser irradiation reduced cellular protein damage (protein carbonyl groups) produced by biological oxidant HOCl.

Eksp Klin Gastroenterol. 2004;(4):29-32, 108.

State of humoral immunity and phagocytic activity of neutrophils in patients with ulcer and effect of low-intensity laser therapy

 

[Article in Russian]

Burduli NM, Gutnova SK.

Abstract

The aim of our investigation was to study the influence of low-intensity laser therapy at the immunologic parameters and Helicobacter pylori (HP) microbial contamination in patients with exacerbation of peptic and duodenal ulcer. 100 patients aged 18-65 were examined and divided into 2 groups. The experimental group (75 patients) underwent a complex drug and laser therapy of various therapeutic techniques. The control group (25 patients) underwent only drug therapy. The results of this study show the immunocorrective effect of different methods of low-intensity laser therapy in the exacerbation period and more essential decrease of HP microbial contamination in the experimental group.

Med Pregl. 2003 Nov-Dec;56(11-12):516-20.

[Laser biostimulation in the treatment of pleurisy]

[Article in Serbian]

Milojevi? M, Kuruc V.

Institut za plu?ne bolesti, Sremska Kamenica, Medicinski fakultet, Novi Sad. drmilojevic@yahoo.com

INTRODUCTION: Low-intensity lasers have been utilized in medicine in two ways: for local stimulation and for stimulation of acupuncture points. Literature data reveal that this method has been indiscriminately applied in psychiatry, rheumatology, gynecology, dermatology, otorhinolaryngology, in diverse acute and chronic pains, inflammations, vascular disorders, angina pectoris, bronchial asthma. Most commonly reported clinical effects are analgesia, spasmolytic and anti-inflammatory effects, as well as faster wound and bone healing. MATERIAL AND METHODS: This prospective study analyses effects of laser biostimulation on patients with pleurisy. The analysis included 25 patients treated at the Institute of Lung Diseases in Sremska Kamenica during 2000, 2001 and 2002. Apart from conservative treatment, these patients were treated with laser biostimulation of acupuncture points and local region for ten days. During treatment, changes of present clinical signs, general symptoms, radiological findings, as well as changes of some relevant biochemical parameters were recorded. RESULTS: Results were compared with the control group which included the same number of patients, who differed from the examined group only by not being exposed to laser biostimulation. The examined group of patients with pleuritis presented with quicker resorption of pleural effusion, less pleural adhesions, more significant decrease of clinical symptoms, especially pain, as well as more significant increase of cortisol and immunoglobulin A and decrease of circulating immune complexes (CIC), leukocytes and sedimentation rate than the control group. DISCUSSION: Mechanisms of laser biostimulation in treatment of pleurisy were described in detail and the obtained results were correlated to those reported by other authors. CONCLUSION: 1. Patients with pleurisy undergoing laser stimulation presented with faster resorption of effusion and remission of the subjective symptoms, as well as significant decrease of biochemical acute inflammation parameters in the peripheral blood and therefore with faster recovery. 2. In patients with pleurisy laser treatment increases regenerative mechanisms of the pleural surface, thus decreasing the quantity of formed adhesions and resulting in better mobility of the diaphragm.

Eksp Klin Gastroenterol. 2002;(2):58-61, 103.

[Changes in local humoral immunity during stomach ulcer healing with laser and drug therapy]

[Article in Russian]

Sokolova GN, Tsaregorodtseva TM, Zotina MM.

Central Research Institute of Gastroenterology, Moscow.

Abstract

The increase of the contents of serum IgA, IgG, IgM on the edge of long non-cicatrizing gastric ulcer was determined. At the same time the level of SIgA decreased in comparison with unaltered gastric mucosa. It is shown that the immunoglobulin content in the healed ulcer cicatrice depended on treatment method. The medicamentous therapy was accompanied by lowering of the contents of IgG, IgA, SIgA and by some increase of IgM level. The laser therapy is characterized by lowering of IgA, IgG, IgM level on a background of significant increase of SIgA content. The local humoral immunity after laser therapy was the same as in persons with unaltered gastric mucosa.

Eksp Klin Farmakol. 2002 Jan-Feb;65(1):58-61.

[Effects of riboxin, essentiale, and phylloquinone on the immunomodulating and antioxidant effect of laser and magneto-laser irradiation in liver toxicosis induced by gentamycin]

[Article in Russian]

Konoplia NA, Prokopenko LG, Uteshev BS.

Biochemistry Department, Kursk State Medical University, ul. K. Marksa 3a, Kursk, 305033 Russia.

The introduction of gentamycine to Wistar rats leads to the toxic liver damage, suppresses humoral immune response to goat erythrocytes, and induces immunosuppressant properties in erythrocytes (caused by increased lipid peroxidation in their membranes and violated cell energy balance) Under these conditions, a combination of the laser or magneto-laser irradiation with the administration of phylloquinone of riboxin provides for a more effective correction of the immune reaction and antioxidant status as compared to the radiation treatment without drugs or with essential. Elimination of the gentamycine induced immunosuppressant properties of erythrocytes is explained by the ability of phylloquinone and essential to reduce the intensity of lipid peroxidation in the cell membranes and with the ability of riboxin to normalize the cell energy balance. An important factor of immunosuppression development in the case of a toxic liver damage caused by D-galactosamine it the interaction of thrombocytes and light erythrocytes with serum factors. The introduction of essential and riboxin favors this interaction and stimulates the development of immunosuppression in thrombocytes.

Pathophysiology. 2001 Aug;8(1):35-40.

Laser irradiation as a potential pathogenetic method for immunocorrection in rheumatoid arthritis.

Timofeyev VT, Poryadin GV, Goloviznin MV.

Departments of Internal Disease and Pathophysiology, Russian State Medical University, Moscow, Russia

We investigated the immunocorrective and clinical effect in 75 rheumatoid patients treated with intravenous laser blood irradiation. A relation between the positive immunotropic (as well as therapeutic) effect and the pre-existent immune status of each patient was revealed. A well-defined effect was found in patients with a low level of CIC and a normal count of functional-competent T-cells. ILIB provided some symptomatic but unstable relief in patients with a high level of CIC and a high functional activity of T-lymphocytes. There was no effect in patients with a high level of CIC and decreased number of lymphocytes.

Bull Exp Biol Med. 2001 Apr;131(4):399-402.

Healing of bone fractures of rat shin and some immunological indices during magnetic laser therapy and osteosynthesis by the ilizarov method.

Baibekov IM, Khanapiyaev UK.

Laboratory of Pathological Anatomy, V. Vakhidov National Surgery Center; Institute of Traumatology and Orthopedics, Ministry of Health of Uzbekistan, Tashkent.

Abstract

The effect of magnetic and laser therapy on healing of bone fractures and blood levels of T and B lymphocytes was studied in rats during osteosynthesis by the Ilizarov method. Laser therapy induced changes in cells attesting to stimulation of reparative processes and normalization of immunological parameters.

Patol Fiziol Eksp Ter. 2000 Oct-Dec;(4):13-5.

[Immunomodulating and antioxidant effects of magnetic and laser irradiation combined with administration of beta-carotene, essentiale, and riboxine during cold stress]

[Article in Russian]

Prokopenko LG, Bystrova NA.

We studied effects of beta-carotine, essentiale and riboxine on immunometabolic effects induced by laser or magnetic laser radiation in intact rats and rats exposed to immersion cold. We found that combination of laser or magnetic laser radiation with administration of beta-carotine or riboxine more effectively corrected antioxidant status and immunological reactivity than radiation alone or in combination with essentiale.

Urologiia. 2000 Jan-Feb;(1):11-5.

[Low-intensity laser radiation in preoperative preparation of patients with benign prostatic hyperplasia]

[Article in Russian]

Ne?mark AI, Muzalevskaia NI.

Low-intensity laser therapy administered in the form of intravenous blood irradiation, transrectal and transurethral prostatic irradiation and their combination as preoperative preparation and correction of immunity disturbances in patients with benign prostatic hyperplasia (BPH) were studied. The response to the treatment was evaluated by positive changes in the immune status and bacterial contamination of the urine and prostatic tissue. Conventional preoperative preparation (uroantiseptics, antibiotics and phytotherapy) fails to correct signs of T-cell immunodeficiency, depression of phagocytic activity of neutrophils, significantly reduce bacteriurea. Laser therapy as intravenous laser blood radiation acts immunomodulatorily on cellular immunity and normalized the proportion of T-helpers of the first and second order (T-suppressors) and neutrophil phagocytosis. The antibacterial effect of this technique on urinary microflora and prostatic tissue is not very high. Local laser therapy is a potent immunostimulator of T- and B-lymphocytes, increased the index of immunoregulatory cells’ proportion, activated phagocytosis of neutrophils. It has pronounced antibacterial effect against gram-negative urinary microflora and tissue of the prostate. Combined laser therapy produced the highest immunomodulating action on T-lymphocytes and immunostimulating one on B-lymphocytes, potentiated phagocytic ability of neutrophils, elevated index of the immunoregulatory cells, but was unable to correct their imbalance completely. Antibacterial effects of combined laser therapy were the highest, including the bacterial group Proteus-Providencia. Preoperative low-intensity laser therapy of BPH reduced the number of postoperative pyoinflammatory complications, hospital stay, severity of postoperative period.

Radiol Med. 1998 Apr;95(4):303-9.

[Low-level laser therapy in osteoarticular diseases in geriatric patients]

[Article in Italian]

Giavelli S, Fava G, Castronuovo G, Spinoglio L, Galanti A.

Dipartimento di Radiologia e Laserterapia, Istituto Gerontologico Pio Albergo Trivulzio, Milano.

INTRODUCTION: Laser light absorption through the skin causes tissue changes, targeting the nervous, the lymphatic, the circulatory and the immune systems with an antalgic, anti-inflammatory, anti-edemic effect and stimulating tissue repair. Therefore low level laser therapy is now commonly used in numerous rehabilitation centers, including the “Istituto Gerontologico Pio Albergo Trivulzio”, Milan, Italy. However, to activate the treatment program, the basic medical research results must always be considered to choose the best optical wavelength spectrum, technique and dose, for rehabilitative laser therapy. We analyzed the therapeutic effects of different wavelengths and powers in various treatment schedules. In particular, a protocol was designed to test such physical parameters as laser type, doses and individual schedule in different pathologic conditions. We report the results obtained with low level laser therapy in the rehabilitation of geriatric patients, considering the various physical and technical parameters used in our protocol. MATERIAL AND METHODS: We used the following laser equipment: an HeNe laser with 632.8 nm wavelength (Mectronic), a GaAs Laser with 904 nm wavelength (Mectronic) and a CO2 Laser with 10,600 nm wavelength (Etoile). To evaluate the patient clinical status, we use a different form for each involved joint; the laser beam is targeted on the region of interest and irradiation is carried out with the sweeping method or the points technique. Irradiation technique, doses and physical parameters (laser type, wavelength, session dose and number) are indicated on the form. The complete treatment cycle consists of 5 sessions per week–20 sessions in all. At the end of the treatment cycle, the results were scored on a 5-grade semiquantitative scale–excellent, good, fair, poor and no results. We examined 3 groups of patients affected with gonarthrosis (149 patients), lumbar arthrosis (117 patients), and algodystrophy (140 patients) respectively. RESULTS: In gonarthrosis patients, the statistical analysis of the results showed no significant differences between CO2 laser and GaAs laser treatments (p = .975), but significant differences between CO2 laser and HeNe laser treatments (p = .02) and between GaAs laser and HeNe laser treatments (p = .003). In lumbar arthrosis patients treated with GaAs or HeNe laser, significant differences were found between the two laser treatments and the combined sweeping-points techniques appeared to have a positive trend relative to the sweeping method alone, especially in sciatic suffering. In the algodystrophy syndrome, in hemiplegic patients, significant differences were found between CO2 and HeNe laser treatments (p = .026), between high and low CO2 laser doses (p = .024), and between low CO2 laser dose and high HeNe laser dose (p = .006). CONCLUSIONS: Low level laser therapy can be used to treat osteoarticular pain in geriatric patients. To optimize the results, the diagnostic picture must be correct and a treatment program defining the physical parameters used (wavelength, dose and irradiation technique) must also be designed.

Lasers Surg Med. 1997;20(4):451-60.

Helium-neon laser irradiation is not a stressful treatment: a study on heat-shock protein (HSP70) level.

Hashieh IA, Tardieu C, Franquin JC.

Faculte d’Odontologie, Marseille, France.

BACKGROUND AND OBJECTIVE: Helium-neon (He-Ne) laser irradiation has been clinically used to reduce chemotherapy-induced mucositis. This work was designed to find out if this treatment is stressful at the cellular level by studying its effects on the level of the stress-inducible heat shock proteins. STUDY DESIGN/MATERIALS AND METHODS: Human desmodontal and mouse L929 fibroblasts were irradiated using a 60 mW laser by a single application of 1.5 and 3J/cm2 in continuous mode. Heat shock protein level was studied by gel electrophoresis and Western blotting using monoclonal antibodies. RESULTS: He-Ne treatment does not induce heat shock protein synthesis in human desmodontal nor in mouse fibroblasts at the energy densities used in this study. CONCLUSIONS: These results indicate that the treatment is not stressful at the cellular level.

Indian J Exp Biol. 1999 May;37(5):444-9.

 

Immunomodulatory effect of laser on whole body exposure.

Ganju L, Salhan A, Karan D, Chanda S, Srivastava KK.

Defence Institute of Physiology & Allied Sciences, Timarpur, Delhi, India.

All biomedical laser applications are based on the interaction of laser light with biological system. During the past decade considerable evidence has accumulated demonstrating that non-thermal exposure to laser can elicit cellular changes in the immune system. In the present study, we have analyzed the effect of laser on immune response in rats. A group of rats were exposed to 0.225 mu j/cm2 for 90 min for 3 days in specially designed fiberglass chambers. The whole body exposure of rats of He-Ne laser modulated both the humoral and cellular responses to tetanus toxoid stimulation. Plain red light used as a control for red laser light showed an appreciable degree of response as compared to the control groups, but not to the extent of the response to laser. Non-responders turned responders after exposure to laser. There was no response in unimmunized groups when exposed to laser and red light alone. The early and heightened immune response and proliferation of lymphocytes after exposure to laser is suggestive of a complex interaction at the cellular immune response level.

Acta Univ Palacki Olomuc Fac Med. 1996;140:43-6.

In vitro He-Ne laser effect on some immunological functions of the polymorphonuclears and monocytes in rabbits.

Luza J, Hubácek J.

Department of Physiology, Medical Faculty, Palacký University, Olomouc, Czech Republic.

The aim of this study is to evaluate in vitro the effect of Helium-Neon (He-Ne) laser irradiation on the viability, adherence, phagocytic activity of the polymorphonuclears and monocytes. Also the level of metabolic processes in phagocytizing blood cells, monocytes and polymorphonuclears was estimated and evaluated by the INT-test. Evaluation of the leukocyte adherence, the method of MacGregor was used. Phagocytic activity was examined by classical method using microspherical hydrophilic particles (Hema-particles). He-Ne laser in a small dosage (< or = 0.8 J) increases the leukocyte adherence, after higher laser irradiation dosage (> 1.2 J) the leukocyte adherence is decreased. The laser effect on the phagocytic activity of both types of blood cells, polymorphonuclears and monocytes is similar. Small dosage of the laser irradiation increases the phagocytic activity, and after higher laser irradiation phagocytic activity is decreased. Also the changes of the level of metabolic processes in the phagocytizing cells are very similar with the changes of phagocytic activity. The viability of the blood cells examined after higher laser irradiation is gradually decreased.

Keio J Med. 1993 Dec;42(4):180-2.

Possible application of the laser in immunobiology.

Tadakuma T.

Department of Microbiology, School of Medicine, Keio University, Tokyo, Japan.

The human immune system acts a defence mechanism against exogenous or indigenous potentially harmful bodies, such as bacteria and viruses. The major histocompatibility complex (MHC class I and class II antigens) form key elements of legitimate body components, and the organization of MHC molecules allows T-lymphocytes to distinguish between legitimate and foreign bodies. On detection of a foreign component, T-cells activate the necessary pathways for destruction of the foreign body. Occasionally however the system breaks down and the result is a disease of an autoimmune nature. Both visible light and infrared low reactive-level laser therapy (LLLT) has been shown to act on immune system cells in a number of ways, activating the irradiated cells to a higher level of activity. Infrared LLLT has been shown to increase both the phagocytic and chemotactic activity of human leukocytes in vitro, for example. This is an example of photobiological activation. Photobiological cell-specific destruction is also possible using doses of low incident laser energy on cells which have been photosensitized for the specific wavelength of the laser, such as in photodynamic therapy (PDT) for superficial cancers. LLLT has also been shown to act directly and selectively on the autoimmune system, restoring immunocompetence to immunocompetence cells. Although much more research needs to be done, there are enough experimental and clinical data to show that the laser, and LLLT in particular, has a possibly exciting role both in immunobiological therapy for diseases of the immune system, and to activate and boost the normal reaction of the immune system components against harmful foreign bodies.

Eksp Klin Farmakol. 1993 Mar-Apr;56(2):42-3.

[The enhancement of immune suppression by local laser irradiation in rats exposed to cyclophosphane]

[Article in Russian]

Konchugova TV, Pershin SB, Minenkov AA.

The authors experimentally studied where low-energy laser radiation (LELR) can be used to enhance cyclophosphanum-induced immunodepression. Preliminary LELR of the adrenal region and cyclophosphanum, 4 mg/kg, resulted in a more profound decrease in the intensity of a primary immune response as compared to the controls received a pseudoradiation and the cytostatic in the same dosage. The findings suggest that laser radiation can be applied to the adrenal region in the clinical setting to reduce a dose of the cytostatic administered and hence adverse effects, by preserving the therapeutical level of immunodepression.

Probl Tuberk. 1991;(6):26-9.

[Effect of low-energy laser irradiation of bronchial mucosa on systemic and local immunity in patients with chronic bronchitis]

[Article in Russian]

Ivaniuta OM, Chernushenko EF, Dzublik AIa, Tyshko NA, Naida IV, Kulik IV.

The effectiveness of endobronchial low-energy laser therapy was studied in 28 patients with chronic nonobstructive bronchitis concurrent with thinning of bronchial mucosa. The course of treatment made it possible to obtain positive dynamics of most parameters of immunologic reactivity in CNB patients. Systemic immunity parameters, except for the NST and concentration of circulating immune complexes, underwent essential normalization. Marked positive changes were found in the parameters characterizing functional activity of alveolar macrophages: there was a 2.5-fold increase in adhesive properties and over 1.3-fold increase in the percentage of phagocytes. The level of secretory IgA rose significantly (by 3.5 times). Hence, a manifested therapeutic effect of this therapeutic method is mainly associated with its immune-stimulating action.

J Photochem Photobiol B. 1992 Dec;16(3-4):347-55.

Cytokine production after helium-neon laser irradiation in cultures of human peripheral blood mononuclear cells.

Funk JO, Kruse A, Kirchner H.

Institute of Immunology and Transfusion Medicine, University of Lubeck Medical School, Germany.

The effects of laser light on the immune system have not been extensively characterized. Low-power laser sources, such as the helium-neon (He-Ne) laser with a wavelength of 632.8 nm, have been found to produce photobiological effects with evidence of interference with immunological functions. We have investigated the effects of He-Ne laser irradiation on Ficoll-Hypaque-isolated human peripheral blood mononuclear cells (PBMC). Cultured cells were irradiated for various times at two selected intensities and then stimulated with different mitogens. The rate of incorporation of 3H-thymidine into the DNA of stimulated cells decreased with increasing energy density. The levels of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in supernatants of the cultures were determined (irradiated either before or after stimulation). When stimulating cells after irradiation, significantly increased levels of all cytokines were detected after 30 min of irradiation (18.9 J cm-2), whereas after 60 min of irradiation (37.8 J cm-2) cytokine levels were found to be significantly decreased.

Bull Exp Biol Med. 2001 Apr;131(4):399-402.

 

Healing of bone fractures of rat shin and some immunological indices during magnetic laser therapy and osteosynthesis by the ilizarolv method

Baibekov IM, Khanapiyaev UK.

Laboratory of Pathological Anatomy, V. Vakhidov National Surgery Center; Institute of Traumatology and Orthopedics, Ministry of Health of Uzbekistan, Tashkent.

The effect of magnetic and laser therapy on healing of bone fractures and blood levels of T and B lymphocytes was studied in rats during osteosynthesis by the Ilizarov method. Laser therapy induced changes in cells attesting to stimulation of reparative processes and normalization of immunological parameters.

Zh Vopr Neirokhir Im N N Burdenko. 1999 Jan-Mar;(1):20-5.

 

The possibility of immunocorrection in spinal-spinal cord trauma by using intravenous laser irradiation

[Article in Russian]

Stupak VV, Rodiukova EN.

The natural defense factors of the body and the cell factors of immunity were studied in 60 patients with acute and early spinal trauma. Immunodeficiency develops in 100% of cases with acute and early spinal trauma. Blood intravenous laser radiation at wave lengths of 632 and 830 nm was shown to produce an immunostimulating effect.

Zh Nevropatol Psikhiatr Im S S Korsakova. 1996;96(2):34-8.

 

The effect of endovascular laser therapy and antioxidants on the immune status and energy metabolism of patients with treatment-resistant forms of schizophrenia

[Article in Russian]

Kut’ko II, Frolov VM, Pustovoi IuG, Pavlenko VV, Rachkauskas GS.

The influence of endovascular laser therapy and of antioxidants on clinical immunological indices and energy metabolism was analysed in 148 schizophrenic patients including 86 patients with shift-like progredient (first group) and 62 patients with continuous-progredient (second group) forms of the disease. Positive trends in psychosis course were observed in 57% of cases in the first group and in 41.9% of patients of the second group. Pronounced improvement of the immunological indices was observed in patients with positive clinical dynamics: decreased peripheral blood immunocytes sensitization to the brain, hepatic, thymus tissue antigens as well as ATP elevation which was evidence of the improvement of energy metabolism.

Keio J Med. 1993 Dec;42(4):180-2.

Possible application of the laser in immunobiology.

Tadakuma T.

Department of Microbiology, School of Medicine, Keio University, Tokyo, Japan.

The human immune system acts a defence mechanism against exogenous or indigenous potentially harmful bodies, such as bacteria and viruses. The major histocompatibility complex (MHC class I and class II antigens) form key elements of legitimate body components, and the organization of MHC molecules allows T-lymphocytes to distinguish between legitimate and foreign bodies. On detection of a foreign component, T-cells activate the necessary pathways for destruction of the foreign body. Occasionally however the system breaks down and the result is a disease of an autoimmune nature. Both visible light and infrared low reactive-level laser therapy (LLLT) has been shown to act on immune system cells in a number of ways, activating the irradiated cells to a higher level of activity. Infrared LLLT has been shown to increase both the phagocytic and chemotactic activity of human leukocytes in vitro, for example. This is an example of photobiological activation. Photobiological cell-specific destruction is also possible using doses of low incident laser energy on cells which have been photosensitized for the specific wavelength of the laser, such as in photodynamic therapy (PDT) for superficial cancers. LLLT has also been shown to act directly and selectively on the autoimmune system, restoring immunocompetence to immunocompetence cells. Although much more research needs to be done, there are enough experimental and clinical data to show that the laser, and LLLT in particular, has a possibly exciting role both in immunobiological therapy for diseases of the immune system, and to activate and boost the normal reaction of the immune system components against harmful foreign bodies.

Probl Tuberk. 1991;(6):26-9.

Effect of low-energy laser irradiation of bronchial mucosa on systemic and local immunity in patients with chronic bronchitis

[Article in Russian]

Ivaniuta OM, Chernushenko EF, Dzublik AIa, Tyshko NA, Naida IV, Kulik IV.

The effectiveness of endobronchial low-energy laser therapy was studied in 28 patients with chronic nonobstructive bronchitis concurrent with thinning of bronchial mucosa. The course of treatment made it possible to obtain positive dynamics of most parameters of immunologic reactivity in CNB patients. Systemic immunity parameters, except for the NST and concentration of circulating immune complexes, underwent essential normalization. Marked positive changes were found in the parameters characterizing functional activity of alveolar macrophages: there was a 2.5-fold increase in adhesive properties and over 1.3-fold increase in the percentage of phagocytes. The level of secretory IgA rose significantly (by 3.5 times). Hence, a manifested therapeutic effect of this therapeutic method is mainly associated with its immune-stimulating action.