PERSISTENT EXPRESSION OF CYTOKINE IN THE CHRONIC STAGE OF VIRAL MYOCARDITIS IN MICE

Background Dilated cardiomyopathy (DCM) is one of the most frequent ca uses of heart failure of unknown origin. One possible cause of DCM is considered to be a sequel to myocarditis. However, the mechanism of pr ogression from viral myocarditis to DCM is still not clear. Methods an d Results The expression of the immunoregulatory cytokines interferon (IFN)-gamma and interleukin (IL)-2 and the proinflammatory cytokines I L-1 beta and tumor necrosis factor (TNF)-alpha in the heart tissue was studied in a murine model of postmyocarditis DCM induced by encephalo myocarditis 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 se en 7 days after inoculation. The expression of these cytokine genes de creased 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 an alysis revealed that some of the mononuclear cells, endothelial cells, and interstitial macrophages were positive for IL-1 beta or TNF-alpha and fibroblasts were positive for IL-1 beta in the heart tissue of mi ce 80 days after inoculation. Conclusions Persistent expression of cyt okines was seen in a murine model of postmyocarditis DCM. These cytoki nes may have important implications in the pathogenesis of DCM.