Persistent expression of cytokine in the chronic stage of viral myocarditis in mice

Circulation
T ShioiS Sasayama

Abstract

Dilated cardiomyopathy (DCM) is one of the most frequent causes of heart failure of unknown origin. One possible cause of DCM is considered to be a sequel to myocarditis. However, the mechanism of progression from viral myocarditis to DCM is still not clear. The expression of the immunoregulatory cytokines interferon (IFN)-gamma and interleukin (IL)-2 and the proinflammatory cytokines IL-1 beta and tumor necrosis factor (TNF)-alpha in the heart tissue was studied in a murine model of postmyocarditis DCM induced by encephalomyocarditis virus. IFN-gamma, IL-1 beta, and TNF-alpha mRNA increased 3 days after virus inoculation. IL-2 mRNA was detectable 7 days after inoculation. The peak expression of all cytokine genes examined was seen 7 days after inoculation. The expression of these cytokine genes decreased thereafter but persisted 80 days after inoculation. IL-1 beta gene expression in the chronic stage was relatively high compared with other cytokines and was correlated with the ratio of heart weight to body weight and the extent of fibrotic lesions. Immunohistochemical analysis revealed that some of the mononuclear cells, endothelial cells, and interstitial macrophages were positive for IL-1 beta or TNF-alpha and fibroblasts w...Continue Reading

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