重型病毒性肝炎患者PBMCs中TNF-α、IL-1α和IL-4mRNA表达水平及其意义探讨

The expression levels of TNF α、IL 1α and IL 4 mRNA in PBMCs and their significance in severe viral hepatitis

本实验应用半定量ＲＴ－ＰＣＲ检测了８例急重肝、１３例亚急重肝和１６例慢重肝患者ＰＢＭＣｓＴＮＦ－α、ＩＬ－１α和ＩＬ－４ｍＲＮＡ的表达水平并对其意义进行了探讨。结果表明，急重肝和亚急重肝患者ＰＢＭＣｓＴＮＦ－α和ＩＬ－１αｍＲＮＡ的表达水平较正常人明显增高，且与内毒素血症和病情轻重相关，而慢重肝仅ＴＮＦ－αｍＲＮＡ略增高，提示ＴＮＦ－α和ＩＬ－１α在急重肝和亚急重肝的发病机理中可能起重要的作用，而在慢重肝的作用可能不是主要的。虽然三型重型肝炎患者ＩＬ－４ｍＲＮＡ的表达水平与正常人比较无显著差异，但急重肝和亚急重肝患者ＩＬ－４ｍＲＮＡ／ＴＮＦ－αｍＲＮＡ和ＩＬ－４ｍＲＮＡ／ＩＬ－１αｍＲＮＡ的比值均明显低于正常人，表明急重肝和亚急重肝患者炎症细胞因子和抗炎症细胞因子调节网络严重失调，ＩＬ－４水平相对低下可能是急重肝和亚急重肝患者ＴＮＦ－α和ＩＬ－１α异常增高的原因之一。

The expression levels of TNF α、IL 1α and IL 4 mRNA in PBMCs after exposure to LPS were measured by semiquantitative RT PCR in 8 patients with fulminant hepatitis,13 patients with subfulminant hepatitis,16 patients with chronic severe hepatitis and 10 normal persons.The results indicated that the production of TNF α and IL 1α mRNA by PBMCs from patients with fulminant and subfulminant hepatitis were greatly enhanced as compared with that of normal controls and the expression levels of TNF α and IL 1α mRNA correlated significantly with the concentration of serum bilirubin,the degree of endotoximia and the prognosis.Whereas only the slight increase of TNF α mRNA was found in chronic severe hepatitis.These suggests that TNF α and IL 1α appear to play an important role in the immune response of fulminant and subfulminant hepatitis and the effects of both cytokines on the pathogenesis of chronic severe hepatitis may be different.Although there was no difference in the expression level of IL 4 mRNA among cases with fulminant,subfulminant,chronic severe hepatitis and normal controls,the ratios of both IL 4 mRNA/TNF α mRNA and IL 4 mRNA/IL 1α mRNA in fulminant and subfulminant hepatitis cases were lower than that in normal controls.The regulation networks of the proinflammatory and anti proinflammatory cytokines seemed markedly disturbed and the IL 4 relatively decreased.Thus we hypothesize that one of the mechanisms by which TNF α and IL 1α overexpress in fulminant and subfulminant hepatitis cases is that the production of both cytokines by PBMCs can not be effectively down regulated by IL 4.