Adenosine inhibits lipopolysaccharide-induced secretion of tumor necrosis factor-α in the failing human heart

Abstract

Background-The proinflammatory cytokine tumor necrosis factor-α (TNF- α) has been implicated in the pathogenesis of congestive heart failure. Recent studies have shown that adenosine inhibits lipopolysaccharide (LPS)- induced expression of TNF-α in macrophages and rat cardiomyocytes. The aim of this study was to determine whether adenosine has a similar effect in the failing human heart. 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-α release in the supernatant was measured with ELISA, and muscle sections were stained for TNF-α. Muscle strips released TNF-α in the absence of LPS (0.22±0.05 pg · mL-1 · mg wet wt-1). TNF-α was immunolocalized to the cardiac myocyte, suggesting that the myocyte is a source for TNF-α production. Adenosine (10 μmol/L) decreased TNF-α by 40% (P