Carvedilol increases the production of interleukin-12 and interferon-gamma and improves the survival of mice infected with the encephalomyocarditis virus.
OBJECTIVE
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 beta-adrenergic receptors, suggesting that beta-adrenergic blockers could modulate the production of cytokines and exert a therapeutic effect in viral myocarditis by blocking the beta-stimulating action of endogenous catecholamines. In clinical trials, the third-generation, nonselective beta-blocker carvedilol was the first among several beta-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 beta(1)-blocker metoprolol, and the nonselective beta-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)-gamma, whereas reducing myocardial virus replication. Propranolol also attenuated myocardial lesions, but to a lesser extent, and increased IL-12 and IFN-gamma levels. Metoprolol had no effect in this model. Encephalomyocarditis virus infection increased plasma catecholamine levels.


CONCLUSIONS
These results suggest that by blocking the beta(2)-stimulating effects of catecholamines, carvedilol exerts some of its beneficial effects by increasing the production of IL-12 and IFN-gamma. Carvedilol may be effective in patients with viral myocarditis by boosting IL-12 and IFN-gamma production.
Nishio
Ryosuke
R
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan.
Shioi
Tetsuo
T
Sasayama
Shigetake
S
Matsumori
Akira
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D018188:Cardiovirus Infections / Q000150:complications*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004686:Encephalomyocarditis virus; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000188:drug therapy / Q000378:metabolism* / Q000821:virology; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology; D015996:Survival Rate
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D018664:Interleukin-12; D007371:Interferon-gamma; D011433:Propranolol; D008790:Metoprolol