The role of proinflammatory cytokines in the development and progression of viral myocarditis

点击翻译按钮获取中文摘要

It is widely accepted that proinflammatory cytokines, such as interferon-γ(IFN-γ), tumor necrosis factor-α(TNF-α) and interleukin-1 (IL-1), are expressed in the heart with viral myocarditis and their expression modifies the condition of the disease, but their role in viral myocarditis is still unclear. We examined the role of proinflammatory cytokines in viral myocarditis using cytokine-knockout (KO) mice. The following results were obtained:(1) IFN-γ KO mice showed increased mortality after the inoculation of encephalomyocarditis virus (EMCV, 500 PFU) compared with wild-type (WT) mice. Cellular infiltration and necrosis in the myocardium were significantly increased in IFN-γ KO mice. These results indicate that IFN-γ has protective action against viral myocarditis.(2) The survival rate of TNF-α KO mice after the inoculation of EMCV (50 or 500 PFU) was significantly lower than that of WT mice. The viral titer and viral genomic RNA of EMCV in the myocardium were significantly higher in TNF-α KO than in WT mice. Intravenous injection of recombinant human TNF-α improved the survival of TNF-α KO mice. Histopathological study revealed that cellular infiltration and ICAM-1 immunoreactivity were significantly reduced in TNF-α KO mice. Thus, TNF-α is thought to have protective action against viral myocarditis via inducing adhesion molecule expression and leukocyte recruitment.(3) The survival rate of IL-1α KO and IL-1αβ KO mice after the inoculation of EMCV (500 PFU) did not differ from that of WT mice. Histopathological findings in IL-1 KO mice were also same as that in WT mice, indicating that IL-1 has no effect on viral myocarditis.