D R Murray1, S D Prabhu, B Chandrasekar. 1. Department of Medicine/Cardiology, University of Texas Health Science Center at San Antonio, South Texas Veterans Healthcare System-Audie Murphy Division, San Antonio, Texas, USA. murrayd@uthscsa.edu
Abstract
BACKGROUND: The sympathetic nervous system and proinflammatory cytokines are believed to play key roles in the pathophysiology of congestive heart failure. To evaluate a possible relationship between these neurohormonal systems, we studied the effects of chronic beta-adrenergic stimulation on the myocardial and systemic elaboration of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. METHODS AND RESULTS: Male rats received either L-isoproterenol (2.4 mg. kg(-1). d(-1), n=8) or saline (n=7) via miniosmotic pumps for 7 days. Myocardial cytokine expression was analyzed by both Northern and Western blotting and localized in the tissue using immunohistochemistry. ELISA was performed to measure circulating levels of cytokines. In myocardium from control animals, neither TNF-alpha nor IL-1beta were detected, whereas IL-6 was present at very low levels. Isoproterenol led to a significant (P<0.01) increase in mRNA and protein expression of all 3 cytokines. Immunohistochemistry did not detect immunoreactivity for either cytokine in myocardium from controls; however, all 3 cytokines were readily detected (P<0.05) throughout the myocardium, localized to resident cells and vessels, in animals treated with isoproterenol. Neither treatment group had detectable levels of cytokines in the serum. CONCLUSIONS: Chronic beta-adrenergic stimulation induces myocardial, but not systemic, elaboration of TNF-alpha, IL-1beta, and IL-6.
BACKGROUND: The sympathetic nervous system and proinflammatory cytokines are believed to play key roles in the pathophysiology of congestive heart failure. To evaluate a possible relationship between these neurohormonal systems, we studied the effects of chronic beta-adrenergic stimulation on the myocardial and systemic elaboration of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. METHODS AND RESULTS: Male rats received either L-isoproterenol (2.4 mg. kg(-1). d(-1), n=8) or saline (n=7) via miniosmotic pumps for 7 days. Myocardial cytokine expression was analyzed by both Northern and Western blotting and localized in the tissue using immunohistochemistry. ELISA was performed to measure circulating levels of cytokines. In myocardium from control animals, neither TNF-alpha nor IL-1beta were detected, whereas IL-6 was present at very low levels. Isoproterenol led to a significant (P<0.01) increase in mRNA and protein expression of all 3 cytokines. Immunohistochemistry did not detect immunoreactivity for either cytokine in myocardium from controls; however, all 3 cytokines were readily detected (P<0.05) throughout the myocardium, localized to resident cells and vessels, in animals treated with isoproterenol. Neither treatment group had detectable levels of cytokines in the serum. CONCLUSIONS: Chronic beta-adrenergic stimulation induces myocardial, but not systemic, elaboration of TNF-alpha, IL-1beta, and IL-6.
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