The Effects Of IL-17A On Myocardial Inflammation And Fibrosis In Mice With Viral Myocarditis

Objective: Balb/c mice of genetic deletion of IL-17A (IL-17A-/-) wereintraperitoneally (i.p) injected with coxsackie virus B3(CVB3) forestablishing VMC models, then to investigate whether IL-17A wouldpromote the inflammation and fibrosis of myocardium in mice with VMC,and to evaluate primarily the contribution of IL-17A signaling to relatedcytokines expression within the heart during the development of VMC.Methods: Specific pathogen-free IL-17A-/-(N=24) and wild-type(WT)(N=32) mice on the Balb/c background were randomly divided intofour different subgroups（IL-17A-/-subgroup n=6、WT subgroup n=8） byrandom number method, then mice were intraperitoneally (i.p) injected with0.1ml100TCID50coxsackie virus B3(CVB3) for establishing VMC models.All surviving mice were separately sacrificed, and the cardiac tissues ofmice were collected on days0,14,28and42after CVB3infection. H&Eand Masson staining were performed for histological analysis. Furthermore,myocardial histopathologic scores and collagen volume fraction (CVF) werecalculated. The expression of cytokines within the blood was detected byprotein chip technology at14day in the period of acute viral myocarditis.Cardiac protein and mRNA levels of TGF-β1were measured by real-timePCR and ELISA, respectively.Results: Our results showed that WT mice developed more severemyocardial inflammation at14day infected with CVB3, then theinflammation of myocardium attenuated gradually during the course of the VMC.On the contrast, myocardial fibrosis was elevated with thedevelopment of VMC. Compared with the WT mice with VMC, The levelsof cardiac IFN-γ and IL-17F were markedly increased in IL-17A-/-mice atday14. However, the expressions of inflammatory cytokines such as IL-1β、IL-2、IL-4、IL-6、IL-10、IL-12、IL-13、IL-17、IL-22、IL-23、IL-28andTNF-α were drastically decreased in the myocardium of IL-17A-/-mice atthis same time（P<0.05）, while there was no difference of the level ofIL-5、IL-21and MIP-3expression within the hearts between IL-17A-/-miceand WT mice. The expression of TGF-β1was increased obviously at day14after CVB3infection, and then was reduced gradually. Nonetheless, thelevels of TGF-β1expressions at days28and42were still higher than day0.When compared with WT mice, IL-17A-/-mice developed lowermyocardial collagen volume fraction of cardiac tissues and the levels ofTGF-β1mRNA and protein were significantly decreased (P<0.05).Conclusions: Taken together, this study demonstrated that IL-17Adeficiency could alleviate the cardiac inflammation in acute viralmyocarditis through intervention with the other related cytokines. Thus, itmay be a one of important causes that IL-17A-/-ameliorate myocardialfibrosis. In other words, IL-17A may exacerbate myocardial inflammationand fibrosis of mice with VMC. Furthermore, IL-17A may be involved inthe pathogenesis of myocardial fibrosis by inducing TGF-β1in mice withVMC.