title: Interleukin-37 Ameliorates Coxsackievirus B3-induced Viral Myocarditis by Modulating the Th17/Regulatory T cell Immune Response.
abstract: Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle with an excessively activated immune response. Numerous interventions have been investigated for the treatment of myocarditis while success is limited. Interleukin-37 (IL-37), a novel member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. However, the modulatory effect of IL-37 in myocarditis is unknown. In this study, we investigated the immunological regulation of IL-37 in the coxsackievirus B3-induced model of murine viral myocarditis. The results show that IL-37 significantly ameliorates the signs of myocarditis with increased survival rate and bodyweight, improved histological changes, reduced activities of MB isoenzyme of creatine kinase and cardiac troponin I, and a suppressed response of Th17 cells and enhanced response of regulatory T cells (Tregs) in the spleen. Moreover, IL-37 down-regulates the expression of Th17-related cytokines IL-6 and IL-17A, while promoting Treg-related cytokine IL-10 levels in the heart. Therefore, IL-37 may exhibit anti-inflammatory activity in the murine model of myocarditis by regulating the balance between Th17 and Treg cells, thereby providing a possible novel therapeutic target in myocarditis.
authors.affiliation: *Health Cardiovascular Department, Shandong Provincial Hospital, Shandong University, Jinan, PR China; and †Department of Cardiology, Rizhao People's Hospital, Rizhao, PR China.
authors.forename: Bang
authors.initials: B
authors.lastname: An
authors.forename: Xuefei
authors.initials: X
authors.lastname: Liu
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Haitao
authors.initials: H
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity*; D007375:Interleukin-1 / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009200:Myocardial Contraction / Q000187:drug effects; D009205:Myocarditis / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; C556062:IL10 protein, mouse; C098680:Il17a protein, mouse; D007375:Interleukin-1; D020381:Interleukin-17; D015850:Interleukin-6; C577686:interleukin-6, mouse; D016753:Interleukin-10