In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells.
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.
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, Suzhou, 215123, China.
Yadong
Y
Hu
Chunsheng
C
Dong
Yan
Y
Yue
Sidong
S
Xiong
D000818:Animals; D001835:Body Weight; D003402:Creatine Kinase / Q000097:blood; D029822:Enterovirus B, Human / Q000302:isolation & purification*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology; D007274:Injections, Intraperitoneal; D007378:Interleukins / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D009206:Myocardium / Q000473:pathology; D012720:Severity of Illness Index; D016019:Survival Analysis; D058504:Th17 Cells / Q000276:immunology*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D007378:Interleukins; C569375:interleukin-35, mouse; D003402:Creatine Kinase