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

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Abstract

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.

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Acknowledgments

The authors thank Prof. Foo Y. Liew at the University of Glasgow for providing mouse IL-35 expression plasmids. This work was supported by grants from the National Natural Science Foundation of China (81072413, 31270977, 31270973, 31170878), Major State Basic Research Development Program of China (2013CB530501, 2013CB531502), Jiangsu “Pan-Deng” Project (BK2010004), the Natural Science Foundation of the Jiangsu Higher Education Institutions (12KJB310015), Jiangsu “333” Project of Cultivation of High-Level Talents and Jiangsu Provincial Innovative Team, Qing Lan Project of the Jiangsu Higher Education Institutions, Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT-IRT1075). The authors have no conflicting financial interests.

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  1. Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, Suzhou, 215123, China

    Yadong Hu, Chunsheng Dong, Yan Yue & Sidong Xiong

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  1. Yadong Hu
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Correspondence to Sidong Xiong.

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Hu, Y., Dong, C., Yue, Y. et al. In vivo delivery of interleukin-35 relieves coxsackievirus-B3-induced viral myocarditis by inhibiting Th17 cells. Arch Virol 159, 2411–2419 (2014). https://doi.org/10.1007/s00705-014-2098-z

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