The Role And Mechanism Of IL-33 In Coxsackievirus B3 Induced Myocarditis

Viral myocarditis (VMC) is the inflammations caused by eosinophilic myocardial virus infection. Type 3 of Coxsackievirus B group virus (CVB3), which belongs to the Enterovirus of Picornaviridae, is the most common pathogens.The number of myocarditis patients caused by CVB3 infection increased in recent years, especially for the young children. CVB3 infects myocardial cell mainly through the synergistic effect of coxsackie virus-adenovirus receptor (CAR) and the receptor decay accelerating factor (DAR). After entering, viral RNA is released to cytoplasm and replication is initiated with host machinery. There are two reasons accounting for the immune damage of CVB3 infected myocardium. One is the direct lysis of myocytes caused by protease 2A induced dissolution of myocardical cytoskeleton through complement way. Another is the direct damage caused by viral infection. However, there is no effect method available to prevent or treat viral myocarditis. Inteleukine 33(IL-33) belongs to the new kind of Inteleukine-1 superfamily and plays important roles both in innate immune response and in adaptive immune response. Particularly, it has been reported in many of inflamation disease models.However, the role of IL-33 in CVB3 induced myocarditis is not clear.Objective To investigate the role and mechanism of IL-33 in CVB3-induced myocarditis.Methods we constructed the IL-33 up-and down-expression plamids IL-33-Pdisplay and IL-33-PLL3.7 by means of molecular biology. The mice were retro-orbital injected with IL-33 up-and down-expression plasmids one or three days post CVB3 infection. At day7, we used immunological technology to detect the mice physiological and biochemical indexes, for example, cytokine expression by ELISA. Meanwhile, we also observed the mice cardiac function by echocardiogram experiments. Finally, we explored the mechanism of IL-33 in CVB3 induced myocarditis, mainly focused on the polarization of macrophages and the down stream signaling pathway of IL-33.Results we successfully constructed the IL-33 over expression and down expression plasmids.The results showed that IL-33 can alleviate the CVB3 induced myocarditis. We found IL-33 can promote the polarization of macrophages mediated by IL-4. Moreover, our results indicated that IL-33 can activate p38 and inhibit ERK1/2 signaling pathway.Conclusions IL-33 can significantly reduce the myocardial inflammation upon CVB3 infection, and result in improved survival, which is mediated by M2 macrophage polarization through IL-4.