title: Interleukin-27 ameliorates coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells.
abstract: BACKGROUND
  Interleukin (IL)-27, which has both pro and anti- inflammatory properties, is a new discovered heterodimeric cytokine that belongs to IL-12 family. However, the expression pattern and functional role of IL-27 in viral myocarditis (VMC) has not been investigated.
  
  
  METHODS
  BALB/c mice were intraperitoneally (i.p) infected with Coxsackie virus B3 (CVB3) for establishing VMC models. Mice were then injected i.p. with Anti-Mouse IL-27 p28Ab or recombinant IL-27 for neutralization and overexpression of IL-27. The survival rates of mice were recorded and the kinetics of IL-27 expression, the frequencies of Th17 cells and the expression of inflammatory cytokine in CVB3-infected mice were determined by ELISA, real-time PCR and flow cytometry.
  
  
  RESULTS
  The IL-27 expression in heart tissues and serum in coxsackievirus B3 (CVB3)-induced myocarditis mice peaked on day 4 but then rapidly decreased during the late infectious stage of CVB3, high IL-27 levels were negatively correlated with bodyweight loss (r = -0.71, P = 0.021) and myocardial pathological score (r = -0.85, P = 0.0018). Additionally, neutralization of IL-27 with Anti-IL-27 Ab accelerated, whereas systemic administration of recombinant mouse IL-27 ameliorated CVB3-induced myocarditis. The protective role of IL-27 in VMC was reflected by an improved survival rate, increased bodyweights, and reduced pathological scores in Anti-IL-27 group compared with IgG control group. Mechanistic investigations showed that IL-27 inhibited Th17 cells frequencies and IL-17 production, as well as the Th17-related proinflammatory cytokines in heart tissues.
  
  
  CONCLUSIONS
  Our results demonstrate that that IL-27 effectively protects the myocardium from the pathogenesis of CVB3 induced myocarditis, which may be attributable to reduced Th17 production. IL-27 might serve as a novel therapeutic treatment for VMC.
authors.affiliation: Department of Cardiovascular Surgery, Xianyang Hospital of Yan'an University, Xianyang, 712000, Shaanxi, China. redzhu99876@163.com.
authors.forename: Hengshan
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, AnKang Hospital of Traditional Chinese Medicine, Ankang, 725000, Shaanxi, China. louchuan1987606@126.com.
authors.forename: Chuang
authors.initials: C
authors.lastname: Lou
authors.affiliation: Department of Cardiology, Xianyang Hospital of Yan'an University, No 38 Wenlin Raod, Xianyang, 712000, Shaanxi, China. Dr_pliu@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000188:drug therapy*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000276:immunology*; D007155:Immunologic Factors / Q000008:administration & dosage*; D064094:Interleukin-27 / Q000008:administration & dosage*; D008297:Male; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy*; D016019:Survival Analysis; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D064094:Interleukin-27