INHIBITORY EFFECT OF INTERLEUKIN-6 ON VASCULAR SMOOTH-MUSCLE CONTRACTION

Our objective was to investigate the direct effect of interleukin-6 (IL-6) on the vascular smooth muscle contraction. We measured the contraction of endothelium-denuded aortic rings isolated from Sprague-Dawley rats. We also investigated the involvement of vasodilator prostaglandin and guanosine 3',5'-cyclic monophosphate (cGMP) productions in the effect of IL-6 using cultured rat vascular smooth muscle cells (VSMC). Exposing the aortic rings to recombinant murine IL-6 (50 U/ml) for 180 min significantly suppressed the phenylephrine (10(-9)-10(-5) M)-induced contraction. This inhibitory effect of IL-6 on the contraction tended to exhibit a dose-dependent relationship (0.5-50 U/ml). The effect of IL-6 was totally eliminated in the presence of indomethacin (10(-5) M). The release of immunoreactive 6-ketoprostaglandin F-1 alpha from cultured rat VSMC was significantly increased by exposure to IL-6. Intracellular cGMP concentration in VSMC was not affected by IL-6. In conclusion, IL-6 is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle. Its action is endothelium independent and mediated by the increased synthesis of prostacyclin in VSMC.