Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial

Tamiris Silva, Yara Dadalti Fragoso, Maria Fernanda Setúbal Destro Rodrigues, Andréa Oliver Gomes, Fernanda Cordeiro da Silva, Lucas Andreo, Ariane Viana, Daniela de Fátima Teixeira da Silva, Maria Cristina Chavantes, Anna Carolina Ratto Tempestini Horliana, Kátia De Angelis, Alessandro Melo Deana, Luciana Prats Branco, Kristianne Porta Santos Fernandes, Lara Jansiski Motta, Raquel Agnelli Mesquita-Ferrari, Sandra Kalil Bussadori, Tamiris Silva, Yara Dadalti Fragoso, Maria Fernanda Setúbal Destro Rodrigues, Andréa Oliver Gomes, Fernanda Cordeiro da Silva, Lucas Andreo, Ariane Viana, Daniela de Fátima Teixeira da Silva, Maria Cristina Chavantes, Anna Carolina Ratto Tempestini Horliana, Kátia De Angelis, Alessandro Melo Deana, Luciana Prats Branco, Kristianne Porta Santos Fernandes, Lara Jansiski Motta, Raquel Agnelli Mesquita-Ferrari, Sandra Kalil Bussadori

Abstract

Objective: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS.

Methods: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS).

The participants were randomized to two groups: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites.

Results: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein).

Conclusion: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart CONSORT 2010.
Fig 1. Flowchart CONSORT 2010.
Fig 2. Positioning for irradiation.
Fig 2. Positioning for irradiation.
A. Opening of mouth for positioning of laser tip in sublingual region. B. Patient with closed mouth to enable irradiation of sublingual region. C. After palpation of radial artery, laser tip positioned for irradiation.
Fig 3. Physical therapy.
Fig 3. Physical therapy.
1) Feet together for 30 seconds with eyes open and 30 seconds with eyes closed on carpets with different textures; 2) Tandem position for 30 seconds with eyes closed and 30 seconds performing a dual task; 3) Squatting to pick up a ball from a cone, standing up, taking a step and placing the ball on another cone (three repetitions); 4) Sitting on chair with balancing disk and performing dual task of picking up objects from the sides (three times on each side); 5) Walking three meters while answering questions posed by therapist or transporting objects; 6) Two minutes of rest.
Fig 4. Expression of interleukin-10.
Fig 4. Expression of interleukin-10.
Values in both groups before (pre) and after (post) treatment with PBM (p = 0.008, two-way ANOVA).
Fig 5. Nitrite levels.
Fig 5. Nitrite levels.
Values in both groups before (pre) and after (post) treatment with PBM (p = 0.543, two-way repeated-measures ANOVA).
Fig 6. Nitrite levels.
Fig 6. Nitrite levels.
Correlation between EDSS score and nitrite levels. (r = 0.52, p = 0,0542).

References

    1. Chalah MA, Ayache SS. Is there a link between inflammation and fatigue in multiple sclerosis? J Inflamm Res. 2018. June;11:253–64. 10.2147/JIR.S167199
    1. Chitnis T. THE ROLE OF CD4 T CELLS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS. Int Rev Neurobiol. 2007;79:43–72. 10.1016/S0074-7742(07)79003-7
    1. Stępień A. Effects of Interferon β-1a and Interferon β-1b Monotherapies on Selected Serum Cytokines and Nitrite Levels in Patients with Relapsing-Remitting Multiple Sclerosis: A 3-Year Longitudinal Study. Neuroimmunomodulation. 2013;213–22. 10.1159/000348701
    1. Leden RE Von, Cooney SJ, Ferrara TM, Zhao Y, Dalgard CL, Anders JJ, et al. 808 nm Wavelength Light Induces a Dose-Dependent Alteration in Microglial Polarization and Resultant Microglial Induced Neurite Growth. Lasers Surg Med. 2013;263(March):253–63.
    1. Ghasemi M, Fatemi A. Pathologic role of glial nitric oxide in adult and pediatric neuroinflammatory diseases. Neurosci Biobehav Rev [Internet]. 2014;45:168–82. Available from: 10.1016/j.neubiorev.2014.06.002
    1. Gonçalves ED, Souza PS, Lieberknecht V, Giulia SP, Barbosa RI, Silveira PCL, et al. Low-level laser therapy ameliorates disease progression in a mouse model of multiple sclerosis Low-level laser therapy ameliorates disease progression in a mouse model of multiple sclerosis. Autoimmunity. 2015;6934(December).
    1. Zhevago NA, Ph D, Samoilova KA, Ph D. Pro- and Anti-inflammatory Cytokine Content in Human Peripheral Blood after Its Transcutaneous (in Vivo) and Direct (in Vitro) Irradiation with Polychromatic Visible and Infrared Light. Photomed Laser Surg. 2006;24(2):129–39. 10.1089/pho.2006.24.129
    1. Kallaur ANAP,Oliveira SR, Name A, Simão C, Regina E, Almeida DDE, et al. Cytokine profile in relapsing ‑ remitting multiple sclerosis patients and the association between progression and activity of the disease. Mol Med Rep. 2013;1010–20. 10.3892/mmr.2013.1256
    1. Wang K, Song F, Fernandez-escobar A. The Properties of Cytokine in Multiple Sclerosis: Pros and Cons. Am J Med Sci [Internet]. 2018;356:552–60. 10.1016/j.amjms.2018.08.018
    1. Kubsik A, Klimkiewicz R, Janczewska K, Klimkiewicz P. Application of laser radiation and magnetostimulation in therapy of patients with multiple sclerosis. NeuroRehabilitation. 2016;38:183–90. 10.3233/NRE-161309
    1. Kozin MS, Kulakova OG, Favorova OO. Involvement of Mitochondria in Neurodegeneration. Biochemistry. 2018;83(7).
    1. Kwilasz AJ, Grace PM, Serbedzija P, Maier SF, Watkins LR. The therapeutic potential of interleukin-10 in neuroimmune diseases. Neuropharmacology. 2016;96(Pt A):55–69.
    1. Hamblin MR, Hospital MG. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys. 2017;4(3):337–61. 10.3934/biophy.2017.3.337
    1. Muili KA, Gopalakrishnan S, Eells JT, Lyons J. Photobiomodulation Induced by 670 nm Light Ameliorates MOG35-55 Induced EAE in Female C57BL / 6 Mice: A Role for Remediation of Nitrosative Stress. PLoS One. 2013;8(6):1–9.
    1. Monjezi S, Negahban H, Tajali S. Effects of dual-task balance training on postural performance in patients with Multiple Sclerosis: A double-blind, randomized controlled pilot trial. Clin Rehabil. 2016;31(2):234–41. 10.1177/0269215516639735
    1. Mercan F, Kara B, Irem B, Mercan E. Effects of motor-motor and motor-cognitive tasks on balance in patients with multiple sclerosis. Mult Scler Relat Disord [Internet]. 2016;7:85–91. Available from: 10.1016/j.msard.2016.03.015
    1. da Silva T, da Silva FC, Gomes AO, Viana AO, Gonçalves MLL, Rodrigues MFSD, et al. Effect of photobiomodulation treatment in the sublingual, radial artery region, and along the spinal column in individuals with multiple sclerosis. Medicine (Baltimore). 2018;97(19):e0627.
    1. Callesen J, Cattaneo D, Brincks J, Dalgas U. How does strength training and balance training affect gait and fatigue in patients with Multiple Sclerosis? A study protocol of a randomized controlled trial. NeuroRehabilitation. 2018;42:131–42. 10.3233/NRE-172238
    1. Tang X, Lan M, Zhang M, Yao Z. Effect of nitric oxide to axonal degeneration in multiple sclerosis via downregulating monocarboxylate transporter 1 in oligodendrocytes. Nitric Oxide [Internet]. 2017;67:75–80. Available from: 10.1016/j.niox.2017.04.004
    1. Giovannoni G, Heales SJR, Silver NC, Riordan JO, Land JM, Clark JB, et al. Raised serum nitrate and nitrite levels in patients with multiple sclerosis. J Neurol Sci. 1997;145:77–81. 10.1016/s0022-510x(96)00246-8
    1. Muili KA, Gopalakrishnan S, Meyer SL, Eells JT, Lyons J. Amelioration of Experimental Autoimmune Encephalomyelitis in C57BL / 6 Mice by Photobiomodulation Induced by 670 nm Light. PLoS One. 2012;7(1).
    1. Song S, Zhou F, Chen WR. Low-level laser therapy regulates microglial function through Src-mediated signaling pathways: implications for neurodegenerative diseases. J Neuroinflammation [Internet]. 2012;9(1):1.
    1. Wong-riley MTT, Liang HL, Eells JT, Chance B, Henry MM, Buchmann E, et al. Photobiomodulation Directly Benefits Primary Neurons Functionally Inactivated by Toxins. J Biol Chem. 2005;280(6):4761–71. 10.1074/jbc.M409650200
    1. Molina-holgado E, Are A, Vela M, Guaza C. Interleukin-4 and interleukin-10 modulate nuclear factor j B activity and nitric oxide synthase-2 expression in Theiler ‘ s virus-infected brain astrocytes. J Neurochem. 2002;81:1242–52. 10.1046/j.1471-4159.2002.00925.x
    1. Berkowitz S, Achiron A, Gurevich M, Sonis P, Kalron A. Acute effects of aerobic intensities on the cytokine response in women with mild multiple sclerosis. Mult Scler Relat Disord [Internet]. 2019;31(February):82–6.
    1. Wong VL HM. A systematic review of aerobic and resistance exercise and inflammatory markers in people with multiple sclerosis. Behav Pharmacol. 2019;30(8):653–. 10.1097/FBP.0000000000000514
    1. Kjølhede T, Dalgas U, Gade AB, Bjerre M, Stenager E, Petersen T, et al. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis. Scand J Med Sci Sport. 2016;26(7):824–34.
    1. Alvarenga-Filho H, Sacramento PM, Ferreira TB, Hygino J, Abreu JEC, Carvalho SR, et al. Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators. J Neuroimmunol [Internet]. 2016;293:91–9. 10.1016/j.jneuroim.2016.02.014

Source: PubMed

3
Abonnieren