缬沙坦对脂多糖诱导的单核细胞白细胞介素6合成的影响

Effects of Valsartan on Interleukin-6 Synthesis in Monocytes Stimulated by Lipopolysaccharide

目的 :通过研究缬沙坦对脂多糖 (LPS)诱导的正常人外周血单核细胞合成白细胞介素 6 (IL 6 )的影响 ,观察缬沙坦的抗炎作用。方法 :采用密度梯度离心法分离人外周血单核细胞 ,应用酶联免疫吸附试验分别观察LPS刺激单核细胞产生IL 6的时间及剂量效应。结果 :LPS刺激单核细胞IL 6合成呈时间依赖性和剂量依赖性 ,10 μg·L-1LPS诱导IL 6合成开始的时间是 2h ,在 2 4h达高峰 ,其峰值是 16 5 4±76 5ng·L-1。缬沙坦 (10 -6mol·L-1～ 10 -3 mol·L-1)不能抑制 10 μg·L-1LPS诱导的单核细胞IL 6合成。结论 :缬沙坦并不适用于抗细胞因子治疗 ,缬沙坦主要不是通过抗炎效应发挥抗动脉粥样硬化作用。

Objective∶ To evalulate the effect of valsartan on interleukin-6 production in human monocytes stimulated by lipopolysaccharide(LPS), assess the influence of valsartan on monocytes inflammatory reaction. Methods∶ Monocytes were isolated by Ficoll density gradient from blood of healthy volunteers. To measure IL-6 production ( by ELISA) stimulated by 10μg·L -1 LPS at 2 h , 4 h , 8 h , 16 h , 24 h and 1μg·L -1 , 2.5μg·L -1 , 5μg·L -1 ,10μg·L -1 LPS at 24 h , the peak to be compared with which inhibited by valsartan(10 -6 mol·L -1 ～ 10 -3 mol·L -1 ).Results∶ IL-6 could be produced after being stimulated with 10μg·L -1 LPS at 2 h. The effect of LPS was dose-dependent and time-dependent, reaching peak at 24 h. The highest level of monocytes IL-6 was 1654±765ng·L -1 in LPS group. Valsartan(10 -6 mol·L -1 ～ 10 -3 mol·L -1 )could not inhibit IL-6 production induced by 10μg·L -1 LPS.Conclusion∶ It is unlikely that valsartan could be used in anticytokine therapeutic strategies in vivo.The antiatherogenic role of valsartan may not depend on its anti-inflammatory action.