狼疮性肾炎患者外周血中IL-18的表达以及FK506、CsA和DEX的抑制作用

目的 :探讨IL 18在活动性狼疮性肾炎 (LN)患者中的表达以及免疫抑制剂FK5 0 6、环孢霉素A(CsA)和地塞米松 (DEX)对其表达的抑制作用。方法 :取 16例活动性LN患者和 10例正常人空腹静脉全血 ,分为未刺激组、脂多糖 /植物血凝素(LPS/PHA)刺激组、LPS/PHA FK5 0 6组、LPS/PHA CsA组和LPS/PHA DEX组在体外培养 2 4h ,采用ELISA法检测培养上清中IL 18的水平 ,应用半定量的RT PCR检测全血培养细胞中IL 18mRNA的表达 ,以及FK5 0 6、CsA和DEX对其表达的抑制作用。结果 :活动性LN患者全血培养的细胞自发及以LPS/PHA刺激后 ,IL 18mRNA和其蛋白的表达显著高于正常对照组 (P <0 .0 1) ;FK5 0 6、CsA和DEX对LPS/PHA刺激的LN患者全血培养细胞IL 18mRNA及其蛋白表达的抑制作用明显大于对正常对照组的抑制作用。结论 :IL 18在活动性LN患者LN的发病机制中可能起着重要的作用 ,抑制IL 18的产生有望成为活动性LN治疗的一个新途径

IL-18 expression in whole blood cell cultures from active lupus nephritis and the inhibitory effects of FK506,cyclosporin A and Dexamethasone

AIM: To explore the expression of IL-18 in patients with active lupus nephritis(LN) and the inhibitory effects of immunesupressive agents FK506, cyclosporin A (CsA) and dexamethasone(DEX). METHODS: Peripheral blood samples were collected from 16 LN patients and 10 health volunteers and cultured with or without PHA/LPS, PHA/LPS FK506, PHA/LPS CsA, PHA/LPS DEX for 24 hours. The IL-18 level in cultured supernatants and the IL-18 mRNA expression in cultured whole blood cells were detected by ELISA and semi-quantitative RT-PCR respectively, and the inhibitory effects of FK506, CsA and DEX on IL-18 expression were investigated. RESULTS: The expression levels of (IL-18) mRNA and its protein in whole blood cell cultures from LN patients were higher than those in normal control group (P<0.01) either spontaneously or after stimulation with LPS/PHA. FK506, CsA and DEX suppressed significantly the expressions of IL-18 mRNA and its protein (P<0.001) in LPS/PHA-stimulated whole blood cell from LN patients.The inhibitory effects of FK506, CsA and DEX on the IL-18 protein expression in LN patients were stronger than that in normal contral group (P<0.01 or P<0.05). CONCLUSION: IL-18 may play an important role in the pathogenesis of LN and inhibition of IL-18 production may be a useful way to treat LN.