Abstract
Our study aims to verify the potential effects and underlying mechanisms of IL-37 in Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC). VMC model was established by intraperitoneal injection of CVB3 into 6-week-old male balb-c mice on day 0. Each mouse of the IL-37-control group and IL-37-VMC CVB3 groups was intraperitoneally injected with IL-37 on day 4 and day 7. The cardiac function was evaluated by transthoracic echocardiography including LVEF, LVFE, IVSs and IVSd. Myocardial injury was measured by Elisa for serum cTnI. The inflammation infiltration and fibrosis were evaluated by hematoxylin and eosin (HE) staining and Masson staining. The expression levels of NLRP3 inflammasome components in pyroptosis were determined by western blot, Elisa, and immunofluorescent analysis. We also detected the expression of IL-37-IL-1R8 in PBMCs by immunofluorescence after injection with CVB3 and IL-37. Compared with the VMC group, mice received CVB3 and IL-37 have improved cardiac function, reduced inflammation infiltration and fibrosis, and with lower expression of cTnI, IL-1β, IL-18 and NLRP3 inflammasome component. IL-37 weakened the upregulation of GSDMD and phosphorylation of NF-κB p65 induced by CVB3. Exogenous addition of IL-37 with CVB3 further increases the production of IL-37-IL-1R8 -IL-18RA complex in vitro. Our findings indicate that IL-37 alleviates CVB3-induced VMC, which may be produced by inhibiting NLRP3 inflammasome-mediated pyroptosis, NF-κB signaling pathway, and IL-37-IL-1R8 -IL-18RA complex.