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EXPERIMENTAL STUDY

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

^* Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

Manuscript received December 31, 2001; revised manuscript received May 20, 2002, accepted October 4, 2002.

^* Reprint requests and correspondence: Dr. Akira Matsumori, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8397, Japan.
amat{at}kuhp.kyoto-u.ac.jp

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 ß-adrenergic receptors, suggesting that ß-adrenergic blockers could modulate the production of cytokines and exert a therapeutic effect in viral myocarditis by blocking the ß-stimulating action of endogenous catecholamines. In clinical trials, the third-generation, nonselective ß-blocker carvedilol was the first among several ß-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 ß₁-blocker metoprolol, and the nonselective ß-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)-, whereas reducing myocardial virus replication. Propranolol also attenuated myocardial lesions, but to a lesser extent, and increased IL-12 and IFN- levels. Metoprolol had no effect in this model. Encephalomyocarditis virus infection increased plasma catecholamine levels.

CONCLUSIONS: These results suggest that by blocking the ß₂-stimulating effects of catecholamines, carvedilol exerts some of its beneficial effects by increasing the production of IL-12 and IFN-. Carvedilol may be effective in patients with viral myocarditis by boosting IL-12 and IFN- production.

Abbreviations and Acronyms   BW   body weight   EMCV   encephalomyocarditis virus   HW   heart weight   IFN   interferon   IL   interleukin   TNF   tumor necrosis factor

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