Carvedilol increases the production of interleukin-12 and interferon-γ and improves the survival of mice infected with the encephalomyocarditis virus

Abstract

ObjectivesThis study was designed to examine the effects of carvedilol in a murine model of viral myocarditis induced by encephalomyocarditis virus (EMCV) infection. BackgroundCytokines 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. MethodsThis 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. ResultsCarvedilol 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. ConclusionsThese results suggest that by blocking the β2-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.