Napoli J, Bishop G A, McCaughan G W
A. W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, New South Wales, Australia.
Gastroenterology. 1994 Sep;107(3):789-98. doi: 10.1016/0016-5085(94)90128-7.
BACKGROUND/AIMS: The role of cytokines in the pathogenesis of chronic liver disease is unclear. The aim of this study was to identify intrahepatic cytokines at the messenger RNA (mRNA) level in end-stage human cirrhosis.
Cytokine mRNA expression for interleukin (IL) 1 beta, IL-2, IL-6, IL-8, transforming growth factor beta, interferon gamma, and tumor necrosis factor alpha was examined by semiquantitative polymerase chain reaction in 25 human cirrhotic livers and 13 controls. Cellular localization of IL-8 was performed by immunohistochemistry.
The results show that IL-2 (P < 0.0001), IL-6 (P < 0.0001), IL-8 (P < 0.0001), transforming growth factor beta (P < 0.001), and interferon gamma (P < 0.04) were upregulated in human cirrhosis compared with controls. IL-1 beta and interferon gamma mRNA showed increased expression in cirrhotics with autoimmune chronic active hepatitis compared with those with primary biliary cirrhosis. Immunohistochemistry showed that IL-8 protein was expressed by infiltrating cells in portal tracts and fibrotic septae and within hepatic lobules.
It is concluded that there is significant activation of cytokines at the mRNA level in end-stage cirrhosis. This suggests continued immune activation even at the late stages of cirrhosis and may indicate the importance of cytokines in the pathogenesis and progression of chronic liver disease.
背景/目的：细胞因子在慢性肝病发病机制中的作用尚不清楚。本研究旨在确定终末期人类肝硬化患者肝内信使核糖核酸（mRNA）水平的细胞因子。
采用半定量聚合酶链反应检测25例人类肝硬化肝脏和13例对照中白细胞介素（IL）-1β、IL-2、IL-6、IL-8、转化生长因子β、干扰素γ和肿瘤坏死因子α的细胞因子mRNA表达。通过免疫组织化学对IL-8进行细胞定位。
结果显示，与对照组相比，人类肝硬化中IL-2（P<0.0001）、IL-6（P<0.0001）、IL-8（P<0.0001）、转化生长因子β（P<0.001）和干扰素γ（P<0.04）上调。与原发性胆汁性肝硬化患者相比，自身免疫性慢性活动性肝炎肝硬化患者的IL-1β和干扰素γ mRNA表达增加。免疫组织化学显示，IL-8蛋白由汇管区和纤维化间隔以及肝小叶内的浸润细胞表达。
得出结论，终末期肝硬化患者细胞因子在mRNA水平有显著激活。这表明即使在肝硬化晚期仍存在持续的免疫激活，可能提示细胞因子在慢性肝病发病机制和进展中的重要性。
