In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells

Arch Virol. 2014 Sep;159(9):2411-9. doi: 10.1007/s00705-014-2098-z. Epub 2014 May 1.


Interleukin (IL)-35 is a new member of the IL-12 cytokine family. The suppressive role of IL-35 in the immune response to parasitic and bacterial infections and in autoimmunity has been demonstrated in terms of its anti-inflammatory properties. However, the functional role of IL-35 in viral myocarditis has not been investigated. In this study, IL-35 expression was measured in heart tissues with coxsackievirus B3 (CVB3)-induced myocarditis. It was significantly reduced in the late stage of viral infection and correlated negatively with disease severity. To examine the therapeutic role of IL-35 in viral myocarditis, an IL-35-expressing plasmid (pIL-35-FC) was packaged with polyethyleneimine and delivered intraperitoneally to BALB/c male mice before and after CVB3 infection. The severity of myocarditis was assessed 7 days after infection. The in vivo delivery of IL-35 significantly ameliorated the severity of viral myocarditis, reflected in an increased survival rate and increased bodyweights, and reduced serum creatine kinase (CK) and CK-MB activities, cardiac pathological scores, and viral replication. We also show that the overexpression of IL-35 reduced splenic Th17 cells and Th17-related proinflammatory cytokines in heart tissues. In conclusion, our data indicate that IL-35 effectively protects the myocardium from the pathogenesis of CVB3-induced viral myocarditis, which may be attributable to reduced Th17 production. This suggests that supplementation with IL-35 could be a novel therapeutic treatment for viral myocarditis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Creatine Kinase / blood
  • Enterovirus B, Human / isolation & purification*
  • Immunosuppressive Agents / administration & dosage*
  • Immunosuppressive Agents / immunology
  • Injections, Intraperitoneal
  • Interleukins / administration & dosage*
  • Interleukins / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / drug therapy*
  • Myocarditis / pathology*
  • Myocarditis / virology
  • Myocardium / pathology
  • Severity of Illness Index
  • Survival Analysis
  • Th17 Cells / immunology*
  • Treatment Outcome


  • Immunosuppressive Agents
  • Interleukins
  • interleukin-35, mouse
  • Creatine Kinase