Persistent Expression of Cytokine in the Chronic Stage of Viral Myocarditis in Mice

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Abstract
Background 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. Methods and Results The expression of the immunoregulatory cytokines interferon (IFN)-γ and interleukin (IL)-2 and the proinflammatory cytokines IL-1β and tumor necrosis factor (TNF)-α in the heart tissue was studied in a murine model of postmyocarditis DCM induced by encephalomyocarditis virus. IFN-γ, IL-1β, and TNF-α 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-1β 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-1β or TNF-α and fibroblasts were positive for IL-1β in the heart tissue of mice 80 days after inoculation. Conclusions Persistent expression of cytokines was seen in a murine model of postmyocarditis DCM. These cytokines may have important implications in the pathogenesis of DCM.