Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts

Proinflammatory cytokines have been implicated in the pathophysiology of di fferent heart diseases. Recent evidence suggests that interleukin-6 (IL-6) may play a role in mechanisms leading to cardiac hypertrophy. In addition, catecholamines are known to induce cardiac hypertrophy. In the present stud y, we examined whether cardiac fibroblasts may be a potential source of IL- 6 production in the rat heart and whether catecholamines can modulate the I L-6 synthesis. Only a small amount of IL-6 mRNA was detected in unstimulate d rat cardiac fibroblasts. However, a 50-fold increase of IL-6 mRNA was fou nd after stimulation with norepinephrine (NE). Addition of carvedilol, a al pha -and beta -adrenergic receptor antagonist, prevented almost completely the NE-induced synthesis of IL-6 mRNA. Phenylephrine, an alpha -adrenergic agonist, and isoproterenol, a beta -adrenergic agonist, also induced an inc rease in IL-6. However, the stimulation via beta -receptors led to a more p ronounced elevation. These data show that NE increases IL-6 expression in r at cardiac fibroblasts and that IL-6 may play an important autocrine/paracr ine role in cardiac disease states associated with hypertrophy.