The proinflammatory cytokines tumor necrosis factor (TNF)- and interleukin (IL)-6 have been implicated in the development of congestive heart failure. Adenosine inhibits the expression of TNF- and IL-6 in macrophages. We determined the effect of adenosine on cytokine expression in rat cardiomyocytes and trabecular muscles obtained from patients with cardiomyopathy. In myocytes, adenosine suppressed TNF- mRNA by 40% (P < 0.05) and induced a 4.7-fold increase in IL-6 mRNA (P < 0.05) with a twofold increase in IL-6 protein release (P < 0.001). The effect on TNF- could be replicated by A₂ agonist. The effect on IL-6 could be replicated by A₃ agonist, but not by A₁ and A₂ agonists, and was completely suppressed by A₃ antagonist. In human trabecular muscles, A₂ agonist suppressed TNF- mRNA by 60% (P < 0.05), but adenosine had no effect on IL-6. In the failing heart, IL-6 was immunolocalized to inflammatory cells. Thus A₂ and A₃ receptors differentially regulate cardiac expression of TNF- and IL-6. Rat cardiomyocytes and the failing human heart respond differently to adenosine.

interleukin-1; interleukin-6; tumor necrosis factor-; congestive heart failure

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