From the University of Pittsburgh Medical Center, Division of Cardiology
and Division of Neuropathology (V.J.S.), Pittsburgh, Pa.
Correspondence to Arthur M. Feldman, MD, PhD, University of Pittsburgh Medical Center, Division of Cardiology, Scaife Hall S572, 200 Lothrop St, Pittsburgh, PA 15213. E-mail feldma{at}card2.cath.upmc.edu
Background—The proinflammatory cytokine tumor
necrosis factor-
Methods and Results—Left ventricular muscle
strips were obtained from seven patients with end-stage congestive
heart failure undergoing heart transplantation or insertion of a left
ventricular assist device. The muscle strips were incubated
at 37°C in 95% O2/5% CO2 and stimulated
with LPS (10 µg/mL). TNF-
Conclusions—Adenosine can significantly diminish
TNF levels in the failing human heart and may represent a new
pharmacological intervention in congestive heart failure.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Adenosine Inhibits Lipopolysaccharide-Induced Secretion of Tumor Necrosis Factor-
in the Failing Human Heart
(TNF-) has been implicated in the pathogenesis
of congestive heart failure. Recent studies have shown that
adenosine inhibits lipopolysaccharide (LPS)-induced
expression of TNF- in macrophages and rat
cardiomyocytes. The aim of this study was to determine
whether adenosine has a similar effect in the failing human
heart. release in the supernatant was measured
with ELISA, and muscle sections were stained for TNF-. Muscle strips
released TNF- in the absence of LPS (0.22±0.05 pg ·
mL-1 · mg wet wt-1). TNF- was
immunolocalized to the cardiac myocyte, suggesting that the myocyte is
a source for TNF- production. Adenosine (10
µmol/L) decreased TNF- by 40% (P<.05). The
selective adenosine A2 receptor agonist DPMA
(10 µmol/L) decreased TNF- release by 87%
(P<.001), whereas ITu (10 µmol/L), an
adenosine-regulating agent that increases
endogenous adenosine concentration, inhibited
TNF- release by 93% (P<.001).
Key Words: adenosine • tumor necrosis factor- • proteins • heart failure
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