Effects of inflammatory cytokines on vascular tone

Objective: To assess the direct effects of the inflammatory cytokines interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-8 (IL-8) on vascular smooth muscle contraction. Methods: Smooth muscle contractility was studied in the thoracic aorta isolated from male Sprague-Dawley rats. Syntheses of cAMP and nitric oxide (NO) were investigated in cultured rat vascular smooth muscle cells (VSMC). Results: Pretreatment of the rings with IL-6 (10 ng/ml) for 180 min caused a significant inhibition of their contraction in response to 10(-5) M phenylephrine, while IL-2 (10 ng/ml) and IL-8 (100 ng/ml) showed no significant effect on the contraction. The inhibitory effect of IL-6 exhibited a dose-dependency (0.1 similar to 10 ng/ml). In cultured rat VSMC, synthesis of cAMP was increased time-dependently by IL-6, while IL-2 and IL-8 failed to show any significant effects. IL-2, IL-6 and IL-8 did not affect the production of nitrite, a stable metabolite of NO, by VSMC. Conclusions: IL-6, but not IL-2 and IL-8, is a potent inhibitor of vascular contraction, which effect is mediated through the increased cAMP synthesis.