Propranolol ameliorates and epinephrine exacerbates progression of acute and chronic viral myocarditis.
Recent studies point to important interactions between proinflammatory cytokines and neurohumoral mediators in heart failure. Here we investigate the influence of the beta-adrenergic system on cytokines and neurohumoral factors and the sequelae of viral myocarditis. In an experimental model with virus-infected BALB/c mice, we studied the acute and chronic effects of epinephrine and propranolol on myocardial morphology, cytokine gene expression, and survival. BALB/c mice were inoculated with the encephalomyocarditis virus (EMCV) or sham inoculated with saline and followed for 30 days. Epinephrine increased the severity of inflammatory cell infiltration and myocardial necrosis induced by EMCV. Gene expression of TNF-alpha, IL-6, and IL-10 was markedly enhanced by epinephrine in EMCV-inoculated mice. Survival rate after 30 days was reduced to 40% in epinephrine-treated EMCV-inoculated mice compared with 70% in untreated EMCV-inoculated mice (P < 0.05). Treatment with the beta-blocker propranolol significantly decreased mortality, myocardial necrosis, and infiltration of inflammatory cells in EMCV-inoculated mice. Propranolol also suppressed gene expression of TNF-alpha, IL-6, and IL-10. A single dose of epinephrine 120 days after EMCV inoculation caused sudden death in 70% of infected mice; propranolol significantly reduced incidence of death to 33%. These results indicate that acute and chronic stages of viral myocarditis are modulated by the beta-adrenergic system and its interactions with proinflammatory cytokines.
Wang
Ju-Feng
JF
Cardiovascular Division, Department of Medicine, and Harvard Thorndike Research Institute, Harvard Medical School, Boston, MA 02215, USA.
Meissner
Achim
A
Malek
Sohail
S
Chen
Yu
Y
Ke
Qingen
Q
Zhang
Jielin
J
Chu
Victor
V
Hampton
Thomas G
TG
Crumpacker
Clyde S
CS
Abelmann
Walter H
WH
Amende
Ivo
I
Morgan
James P
JP
D000208:Acute Disease; D000322:Adrenergic Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000650:Amnion / Q000166:cytology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000821:virology; D018188:Cardiovirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D004686:Encephalomyocarditis virus; D004837:Epinephrine / Q000494:pharmacology*; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D011433:Propranolol / Q000494:pharmacology*
D000322:Adrenergic Agonists; D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D011433:Propranolol; D004837:Epinephrine