Peng Bing, Liu Shuyun
Department of Obstetrics and Gynecology, Second Huaxi Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Fu Chan Ke Za Zhi. 2002 Sep;37(9):516-8.
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).
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.
(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).
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.
探讨1型辅助性T细胞（TH(1)）细胞因子[干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）]及2型辅助性T细胞（TH(2)）细胞因子[白细胞介素-4（IL-4）]在妊娠期肝内胆汁淤积症（ICP）发病机制中的作用。
采用光血凝素刺激培养20例ICP患者（研究组）及20例正常孕妇（对照组）的外周血单个核细胞（PBMC），用酶联免疫吸附法检测上清液中TNF-α、IFN-γ及IL-4水平。
（1）在PHA诱导培养的PBMC上清液中，研究组IFN-γ、TNF-α水平分别为（639±156）ng/L和（1 021±231）ng/L，显著高于对照组的（464±147）ng/L和（728±175）ng/L（P<0.001）；研究组IL-4水平为（22±4）ng/L，低于对照组的（27±6）ng/L（P<0.05）；（2）上清液中，研究组TNF-α/IL-4比值为48±11，显著高于对照组的30±8，研究组IFN-γ/IL-4比值为30±8，也高于对照组的19±6（P<0.001）；（3）总胆汁酸与TH(1)细胞因子浓度呈显著正相关，相关系数（r）分别为0.458和0.692（P<0.01）。
ICP患者细胞因子谱平衡发生偏移，从TH(1)型反应向TH(2)型反应转变。增强的细胞介导免疫反应扰乱了母胎间的免疫耐受平衡；ICP增强的TH(1)型免疫反应可能导致肝细胞损伤及胆汁淤积的发生。
