title: Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of coxsackievirus b3-induced viral myocarditis reduces myocardium inflammation.
abstract: BACKGROUND
  Recently, some studies indicate that interleukin (IL)-17, known as a T cell (Th17)-derived proinflammatory cytokine, is the major mediator of tissue inflammation in inflammatory and autoimmune diseases. Viral myocarditis (VMC) is a T cell-mediated autoimmune disease, but the role for IL-17 in VMC is not well defined.
  
  
  RESULTS
  Using IL-17 monoclonal antibody (IL-17mAb)-treated VMC mice, we tested the pathogenic role of IL-17 in the development of VMC. VMC mice were treated with monoclonal rat anti-murine IL-17 antibody (anti-IL-17) or rat IgG(2A) isotype control or phosphate-buffered solution 3 days after Coxsackievirus B3 (CVB3) injection. Normal mice without any manipulation were taken as normal control. The survival rates of mice were monitored and heart pathology was examined histologically. IL-17, IL-6, and TNF-α mRNA of the myocardium were assessed by semi-quantitative RT-PCR. Systemic IL-17, IL-6, and TNF-α level were measured by enzyme-linked immunosorbent assay, and local myocardium IL-17 expression was analyzed using immunohistochemical staining. Flow cytometric analysis was used to evaluate the frequencies of Th17 subsets in CD4(+) T cells. Results showed that neutralization of IL-17 with anti-IL-17 can ameliorate clinical symptoms, defer disease course, decrease serum IL-17 level, without declining the IL-17, IL-6 and TNF-α mRNA transcript level and serum IL-6, TNF-α level. The differentiation and proliferation of the Th17 cells were unchanged.
  
  
  CONCLUSIONS
  Our data suggest that IL-17 is crucially involved in the pathogenesis of murine VMC, IL-17 inhibition might ameliorate the myocardium inflammation after the onset of VMC.
authors.affiliation: Guangxi Cardiovascular Institute, Nanning, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fan
authors.forename: Wu
authors.initials: W
authors.lastname: Weifeng
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuluan
authors.forename: Kong
authors.initials: K
authors.lastname: Qing
authors.forename: Pang
authors.initials: P
authors.lastname: Yu
authors.forename: Huang
authors.initials: H
authors.lastname: Yanlan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D057134:Antibodies, Neutralizing / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000008:administration & dosage*; D029822:Enterovirus B, Human / Q000276:immunology / Q000472:pathogenicity*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D009206:Myocardium / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C515934:Il17a protein, rat; D020381:Interleukin-17