Catecholamines stimulate interleukin-6 synthesis in rat cardiac fibroblasts

Proinflammatory cytokines have been implicated in the pathophysiology of different 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 study, we examined whether cardiac fibroblasts may be a potential source of IL-6 production in the rat heart and whether catecholamines can modulate the IL-6 synthesis. Only a small amount of IL-6 mRNA was detected in unstimulated rat cardiac fibroblasts. However, a 50-fold increase of IL-6 mRNA was found after stimulation with norepinephrine (NE). Addition of carvedilol, a alpha -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 increase in IL-6. However, the stimulation via beta -receptors led to a more pronounced elevation. These data show that NE increases IL-6 expression in rat cardiac fibroblasts and that IL-6 may play an important autocrine/paracrine role in cardiac disease states associated with hypertrophy.