Melatonin Contributes to the Seasonality of Multiple Sclerosis Relapses

Abstract

SUMMARY Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the central nervous system. These epidemiological observations suggest that environmental factors influence the disease course. Here we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells as well as boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact on T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

“…Melatonin has been shown to have immunomodulatory properties and was recently implicated in the development of MS 36. While melatonin was not studied with the metabolomics platform used in our study, serotonin levels were not associated with MS risk or disease severity.…”

Vitamin D supplementation differentially affects seasonal multiple sclerosis disease activity

“…The summer peak in relapse rates was explained by higher temperatures leading to immunological modulations, in particularly to a change in leukocyte nitric-oxide production (Beenakker et al, 2001;Oqawa et al, 2004). A complementary immunological explanation from a recently conducted study are the summer troughs of melatonin production, which ultimately lead to the induction of pathogenic Th17-cell differentiation, inhibition of protective T-regulatory cells, and deactivation of IL-10 promotors (Farez et al, 2015). Further studies are warranted to clarify these hypotheses as possible reasons for the increase in relapse rates during summer.…”

Age-Related Changes in the Melatonin and Thymulin Biorhythms as Risk Factors for Human Neurodegenerative Diseases

“…The pineal gland dysfunction may be pathogenetic factor of such immune disturbances. Thus, in MS patient's melatonin decreases the formation of pathogenic Th17 T cells, cytokine interleukin (IL)-17 and stimulates formation of protective Tr1 regulatory cells and anti-inflammatory cytokine IL-10 [55]. We have shown that old organism's response at neurodegenerative pathology (multiple sclerosis) to the influence of neurotrophic factors may be changed [56].…”