INFLAMMATORY CYTOKINES AND RAT VASCULAR TONE

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Abstract
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 3h caused a significant inhibition of its contraction (58.9 ± 7.8%, n= 9, P < 0.01) when induced by 10−6mol/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 10−5mol/L indomethacin. 5. In cultured rat vascular smooth muscle cells (VSMC), the release of 6‐keto‐prostaglandin F1α 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 α‐adrenergic‐stimulated contraction of vascular smooth muscle and its action is mediated by the increased synthesis of prostacyclin rather than NO.