缬沙坦对不同浓度C-反应蛋白诱导的单核细胞白细胞介素-6合成的影响

Effect of valsartan on interleukin-6 synthesis in monocytes stimulated by C-reactive protein

目的通过研究缬沙坦对C-反应蛋白(CRP)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CRP(15、、10及20 mg/L)刺激单核细胞产生IL-6的时间及剂量效应,其峰值与缬沙坦抑制剂进行比较。结果CRP刺激单核细胞IL-6合成呈时间依赖性和剂量依赖性,20 mg/L CRP与5 mg/L CRP诱导IL-6合成开始的时间是4 h,在24 h达高峰,其峰值分别是(904±77)ng/L和(698±52)ng/L。高浓度缬沙坦(≥10-3mol/L)能抑制20 mg/LCRP诱导的单核细胞IL-6合成,较低浓度缬沙坦(1×10-6mol/L^1×10-3mol/L)能抑制5 mg/L CRP诱导的单核细胞IL-6合成。结论缬沙坦可用于轻度炎症时抗细胞因子治疗。

Objectives To evaluate the effect of valsartan on interleukin-6 production in human monocytes stimulated by C-reactive protein（CRP） and to assess the influence of valsartan on monocyte inflammatory reaction. Methods Monocytes were isolated by Fieoll density gradient from blood of healthy volunteers. IL-6 produetion （by ELISA） in monocytes stimulated by 20 mg/L and 5 mg/L CRP was measured at 2 h , 4 h,8 h, 16 h and 24 h. The peak value was compared with IL-6 produced by the monocytes inhibited by valsartan （ 1 × 10^-6 mol/L～ 1 × 10^-3 mol/L）.Results IL-6 began to be synthesized by monocytes stimulated by CRP after stimulation for 4 h. The effect of CRP was dose-dependent and time-dependent, reaching peak at 24 h. The highest levels of monocytes IL-6 were 904 ± 77 and 698 ± 52 ng/L in 20 mg/L and 5 mg/L CRP groups, respectively. Valsartan（ 1 × 10^-3 mol/L） inhibited IL-6 production induced by 20 mg/L CRP and valsartan（ 1 × 10^-6 mol/L- 1 × 10-3 mol/L）could inhibit IL-6 production induced by 5 mg/L CRP. Conclusion Valsaaan could be used in anticytokine therapeutic strategy in low-grade inflammation.