OBJECTIVES: This study was designed to examine the effects of carvedilol in a murine model of viral myocarditis induced by encephalomyocarditis virus (EMCV) infection. BACKGROUND: Cytokines play an important role in the pathophysiology of viral myocarditis. Catecholamines influence the production of cytokines via β-adrenergic receptors, suggesting that β-adrenergic blockers could modulate the production of cytokines and exert a therapeutic effect in viral myocarditis by blocking the β-stimulating action of endogenous catecholamines. In clinical trials, the third-generation, nonselective β-blocker carvedilol was the first among several β-blockers to reduce mortality in heart failure. However, the effects of carvedilol in acute viral myocarditis and on cytokine production are unknown. METHODS: This study compared the effects of carvedilol, the selective β1-blocker metoprolol, and the nonselective β-blocker propranolol in a murine model of viral myocarditis induced by EMCV. RESULTS: Carvedilol improved the 14-day survival of the animals, attenuated myocardial lesions on day 7, and increased myocardial levels of interleukin (IL)-12 and interferon (IFN)-γ, whereas reducing myocardial virus replication. Propranolol also attenuated myocardial lesions, but to a lesser extent, and increased IL-12 and IFN-γ levels. Metoprolol had no effect in this model. Encephalomyocarditis virus infection increased plasma catecholamine levels. CONCLUSIONS: These results suggest that by blocking the β-stimulating effects of catecholamines, carvedilol exerts some of its beneficial effects by increasing the production of IL-12 and IFN-γ. Carvedilol may be effective in patients with viral myocarditis by boosting IL-12 and IFN-γ production. © 2003 by the American College of Cardiology Foundation.
Nishio, R., Shioi, T., Sasayama, S., & Matsumori, A. (2003). Carvedilol increases the production of interleukin-12 and interferon-γ and improves the survival of mice infected with the encephalomyocarditis virus. Journal of the American College of Cardiology, 41(2), 340–345. https://doi.org/10.1016/S0735-1097(02)02711-0