Photobiomodulation with 670nm near infrared light treatment ameliorates disease severity of MOG35-55 induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice.

摘要

Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system (CNS). Disease is mediated by peripheral activation of myelin protein specific CD4+ T cells. Activated CD4+ T cells cross the blood brain barrier, and are secondarily activated in the CNS. CD4+ T cells mediate activation of resident glial cells and infiltration of other peripheral immune cells like B cells and macrophages. Combined effector functions of activated immune cells and glial cells via inflammatory cytokines, proteases, myelin specific autoantibodies, and reactive oxygen species (ROS) or reactive nitrogen species (RNS) play differential roles in disease onset, maintenance and progression. Current and emerging knowledge of MS pathogenesis come from studies of the primary animal model, experimental autoimmune encephalomyelitis (EAE). Studies involving EAE have led to the development of different FDA approved MS medications. While some advances have been made in curtailing immune inflammatory responses in MS, little success have been achieved in preventing or reducing the demyelination and axonal death associated with disease progression. A novel therapeutic approach utilizing photobiomodulation with light [near infrared-light emitting diode (NIR-LED) or low level laser therapy (LLLT); 600-900nm] has demonstrated neuroprotective and immunomodulatory roles in diseases similar to MS pathogenesis.;The goal of this study was to determine the therapeutic efficacy of photobiomodulation with 670nm NIR-LED light treatment for MS using myelin oligodendrocyte glycoprotein (MOG), peptide 35-55-induced EAE in C57BL/6 mice. Our results showed that treating EAE mice with 670nm light reduced clinical disease severity, evident by a more sustained disease recovery. This effect was seen in "preventive" and "treatment" models, that addressed prevention of disease initiation and treating established EAE, respectively. Data showed that, 670nm light ameliorated EAE via modulation of the inflammatory immune response by down-regulation of proinflammatory cytokines (IFNgamma and TNFalpha), with concomitant up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Results presented here demonstrated coordinated immunoregulation and attenuation of nitrosative/oxidative stress as essential factors contributing to clinical disease amelioration by 670nm light treatment in EAE. Furthermore, 670nm light protected CNS cells from apoptosis. Thus, 670nm photobiomodulation may be a effective therapeutic strategy of the treatment of multiple sclerosis.