Inflammatory cytokines and rat vascular tone.

1. Experiments were performed to examine the effect of inflammatory cytokines, interleukin-2 (IL-2), IL-6 and IL-8, on the contractility of rat aorta. 2. Pretreatment of the endothelium-denuded aortic ring with IL-6 for 3 h caused a significant inhibition of its contraction (58.9 +/- 7.8%, n = 9, P < 0.01) when induced by 10(-6) mol/L phenylephrine. 3. On the other hand, IL-2 and IL-8 failed to show significant effects on the contractility of the aorta. 4. This inhibitory effect of IL-6 on phenylephrine-induced contraction showed dose-dependency, and completely disappeared in the presence of 10(-5) mol/L indomethacin. 5. In cultured rat vascular smooth muscle cells (VSMC), the release of 6-keto-prostaglandin F1alpha into the extracellular medium was significantly increased by exposure to IL-6, but not by exposure to IL-2 or IL-8. 6. IL-2, IL-6 and IL-8 showed no effects on the release of nitrite, a stable metabolite of nitric oxide (NO), from VSMC. 7. These results indicate that IL-6, not IL-2 or IL-8, is a potent inhibitor of the alpha-adrenergic-stimulated contraction of vascular smooth muscle and its action is mediated by the increased synthesis of prostacyclin rather than NO.