(Circulation. 2000;101:2338.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Chronic ß-Adrenergic Stimulation Induces Myocardial Proinflammatory Cytokine Expression
From the Department of Medicine/Cardiology, University of Texas Health Science Center at San Antonio, South Texas Veterans Healthcare System–Audie Murphy Division, San Antonio, Tex (D.R.M., B.C.), and the University of Louisville Health Sciences Center, Louisville VA Medical Center, Ky (S.D.P.).
Correspondence to David R. Murray, MD, Department of Medicine/Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-900. E-mail murrayd{at}uthscsa.edu
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 ß-adrenergic stimulation on the
myocardial and systemic elaboration of tumor necrosis factor (TNF)-
,
interleukin (IL)-1ß, 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- nor IL-1ß 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 ß-adrenergic stimulation induces
myocardial, but not systemic, elaboration of TNF-, IL-1ß, and
IL-6.
Key Words: isoproterenol • tumor necrosis factor- • interleukins • sympathetic nervous system • myocardium
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