Abstract

BackgroundInterleukin (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.MethodsBALB/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.ResultsThe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0418-x) contains supplementary material, which is available to authorized users.

Highlights

  • Interleukin (IL)-27, which has both pro and anti- inflammatory properties, is a new discovered heterodimeric cytokine that belongs to IL-12 family

  • IL-27 is a newly discovered heterodimeric cytokine that belongs to IL-12 family, which is composed of the Epstein-Barr virus-induced gene 3 (EBI3) and the p28 subunit [6]

  • Neutralization of IL-27 exacerbated while administration of rmIL-27 alleviated Coxsackie virus B3 (CVB3)-induced myocarditis we examined the protective role of IL-27 against CVB3-induced myocarditis in vivo

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Summary

Introduction

Interleukin (IL)-27, which has both pro and anti- inflammatory properties, is a new discovered heterodimeric cytokine that belongs to IL-12 family. The expression pattern and functional role of IL-27 in viral myocarditis (VMC) has not been investigated. IL-27 is a newly discovered heterodimeric cytokine that belongs to IL-12 family, which is composed of the Epstein-Barr virus-induced gene 3 (EBI3) and the p28 subunit [6]. IL-27 plays a critical role in the early regulation of T helper type 1 initiation, and enhances proliferation of naive CD4+T cells and naive B cells [9,10,11]. Exerts anti-inflammatory functions by inhibiting the development of Th17 cells and inducing IL-10 producing type 1 regulatory T cells [12,13,14]. IL-27 plays both pathogenic and protective roles in given infection and autoimmune disease models

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