辅助性T淋巴细胞亚型与妊娠期肝内胆汁淤积症发病的关系

目的　探讨辅助性T淋巴细胞 (TH) 1型细胞因子 [γ干扰素 (IFN γ)、肿瘤坏死因子α(TNF α) ]及TH2 型细胞因子 [白细胞介素 4(IL 4) ]与妊娠期肝内胆汁淤积症 (ICP)发病的关系 ,从分子免疫学角度探讨ICP的发病机理。方法　采用双抗体夹心酶联免疫吸附法 ,检测 2 0例ICP孕妇 (研究组 )和 2 0例正常妊娠妇女 (对照组 )外周血单个核细胞在植物血凝素刺激下产生TH1型细胞因子(IFN γ ,TNF α)及TH2 型细胞因子 (IL 4)的水平 ,并对TH1型细胞因子与ICP患者血清总胆汁酸的相关性进行分析。结果　 ( 1)研究组孕妇的IFN γ、TNF α水平分别为 ( 63 9± 15 6)ng/L、( 10 2 1± 2 3 1)ng/L ;明显高于对照组孕妇的 ( 464± 147)ng/L、( 72 8± 175 )ng/L ,两组比较 ,差异有极显著性 (P <0 0 0 1)。研究组孕妇的IL 4水平为 ( 2 2± 4)ng/L ,明显低于对照组孕妇的 ( 2 7± 6)ng/L ,两组比较 ,差异有显著性(P <0 0 5 )。 ( 2 )研究组孕妇的TNF α/IL 4比值为 48± 11,明显高于对照组孕妇的 3 0± 8;研究组孕妇的IFN γ/IL 4比值为 3 0± 8,明显高于对照组的 19± 6,两组分别 ,差异均有极显著性 (P <0 0 0 1)。( 3 )研究组孕妇的IFN γ、TNF α水平与ICP患者血清胆汁酸水平呈正相关 ,相关系数 (r)分别为 0 45 8,0

Study of relationship between T helper cell type-1 and type-2 cytokines and intrahepatic cholestasis of pregnancy

OBJECTIVE: To investigate the effect of T helper cell type-1 (TH(1)) cytokines [interferon-gamma (IFN-gamma), tumor necrosis factor-a (TNF-alpha)] and T helper cell type-2 (TH(2)) cytokines [interleukin-4 (IL-4)] on pathogenesis of intrahepatic cholestasis of pregnancy (ICP). METHODS: The peripheral blood mononuclear cells (PBMC) from 20 cases of ICP patients (study group) and 20 cases of normal pregnant women (control group) were cultured with photohemglutinin stimulation. TNF-alpha, IFN-gamma and IL-4 were determined in the supernatant by enzyme- linked-immunoassay. RESULTS: (1) In supernatants of cultured PHA induced PBMC, the levels of IFN-gamma and TNF-alpha of study group were (639 +/- 156) ng/L and (1 021 +/- 231) ng/L, which were significantly higher than those of control group, (464 +/- 147) ng/L and (728 +/- 175) ng/L (P < 0.001); the IL-4 level of study group was (22 +/- 4) ng/L, which was lower than that of control group, (27 +/- 6) ng/L (P < 0.05); (2) In supernatants, the ratio of TNF-alpha/IL-4 of study group was 48 +/- 11, which was significantly higher than that of control group (30 +/- 8), the ratio of IFN-gamma/IL-4 of study group was 30 +/- 8, which was also higher than that of control group (19 +/- 6, P < 0.001); (3) There were significant positive correlations between total bile acid and concentrations of the TH(1) cytokines, the correlation coefficients(r) were 0.458 and 0.692, respectively (P < 0.01). CONCLUSIONS: A shift in the balance of cytokine profiles away from TH(1)-type reactivity to TH(2)-type reactivity occurs in ICP. The enhanced cell-mediated immune reaction disturbs the immune tolerance balance between mother and fetus; The enhanced TH(1)-type immune response of ICP may contribute to the damage of hepatic cells and the occurrence of cholestasis.