title: Melatonin enhances interleukin-10 expression and suppresses chemotaxis to inhibit inflammation in situ and reduce the severity of experimental autoimmune encephalomyelitis.
abstract: Melatonin is the major product secreted by the pineal gland at night and displays multifunctional properties, including immunomodulatory functions. In this study, we investigated the therapeutic effect of melatonin in experimental autoimmune encephalomyelitis (EAE). We demonstrated that melatonin exhibits a therapeutic role by ameliorating the clinical severity and restricting the infiltration of inflammatory Th17 cells into the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced EAE. Furthermore, melatonin enhances splenic interleukin (IL)-10 expression in regulatory T cells by inducing IL-27 expression in the splenic DC; it also suppresses the expression of IFN-γ, IL-17, IL-6, and CCL20 in the CNS and inhibits antigen-specific T cell proliferation. However, there were no significant differences in the percentage of splenic regulatory T cells. These data provide the first evidence that the therapeutic administration of melatonin is effective in mice with EAE and modulates adaptive immunity centrally and peripherally. Thus, we suggest that melatonin could play an adjunct therapeutic role in treating human CNS autoimmune diseases such as multiple sclerosis. Melatonin merits further studies in animals and humans.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shyi-Jou
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jing-Wun
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Department of Neurology, Cheng Hsin General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kai-Chen
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yung-Rong
authors.initials: YR
authors.lastname: Yang
authors.affiliation: Pediatric Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Pi-Fang
authors.initials: PF
authors.lastname: Liu
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address: lingujiun@mail.ndmctsgh.edu.tw.
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C556062:IL10 protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D016753:Interleukin-10; D008550:Melatonin
keywords: Autoimmune disease; Chemokine; Experimental autoimmune encephalomyelitis; Interleukin-10; Interleukin-27; Melatonin; Th17; multiple sclerosis