Llorent L, Richaud-Patin Y, Alcocer-Castillejos N, Ruiz-Soto R, Mercado M A, Orozco H, Gamboa-Domínguez A, Alcocer-Varela J
Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, México.
J Hepatol. 1996 May;24(5):555-63. doi: 10.1016/s0168-8278(96)80140-1.
BACKGROUND/AIMS: In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis.
We assessed the gene expression of interleukins 1 beta, 2, 6, 8, and 10, as well as of tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma by a quantitative polymerase chain reaction.
We found high levels of transforming growth factor-beta in post-hepatitis C liver cirrhosis, high to moderate in alcoholic liver cirrhosis and low in non-cirrhotic specimens. Expression of interleukin-10, tumor necrosis factor-alpha, and interferon-gamma genes was detected in most post-hepatitis C liver cirrhosis, but not in idiopathic portal hypertension or alcoholic liver cirrhosis biopsies. The interleukin1-beta, 6 and 8 gene expression was significantly lower in alcoholic liver cirrhosis compared to post-hepatitis C liver cirrhosis, but higher compared to idiopathic portal hypertension specimens. Thus, post-hepatitis C liver cirrhosis samples showed a high degree of cytokine gene expression, whereas in alcoholic liver cirrhosis it tended to be moderate, and restricted to some cytokines (transforming growth factor-beta, interleukin-1, 6 and 8, but not interleukin-10, tumor necrosis factor-alpha or interferon-gamma). In contrast, most non-cirrhotic specimens showed a restricted and low cytokine gene expression.
These data suggest that transforming growth factor-beta may have an important role in liver fibrosis and inflammation. Interleukin-1 beta, 6, 8, tumor necrosis factor-alpha and interferon-gamma, appear to participate in the pathogenesis of the mild to severe inflammatory phenomena seen in alcoholic and post-hepatitis C liver cirrhosis, respectively. Our data suggest that tumor necrosis factor-alpha does not participate in the hepatocellular damage of alcoholic liver cirrhosis, and indicate that neither interferon-gamma nor interleukin-10, at least at the levels observed in post-hepatitis C liver cirrhosis, are able to counteract the fibrotic/inflammatory process seen in this condition.
背景/目的：为了探究细胞因子在肝硬化发病机制中的作用，我们分析了酒精性肝硬化、丙型肝炎后肝硬化以及无肝硬化的特发性门静脉高压患者肝活检组织中细胞因子的基因表达情况。
我们通过定量聚合酶链反应评估白细胞介素1β、2、6、8和10，以及肿瘤坏死因子-α、转化生长因子-β和干扰素-γ的基因表达。
我们发现丙型肝炎后肝硬化中转化生长因子-β水平较高，酒精性肝硬化中为中度至高度，非肝硬化标本中较低。大多数丙型肝炎后肝硬化中检测到白细胞介素-10、肿瘤坏死因子-α和干扰素-γ基因的表达，但特发性门静脉高压或酒精性肝硬化活检组织中未检测到。与丙型肝炎后肝硬化相比，酒精性肝硬化中白细胞介素1-β、6和8的基因表达显著降低，但与特发性门静脉高压标本相比则较高。因此，丙型肝炎后肝硬化样本显示出高度的细胞因子基因表达，而酒精性肝硬化中则趋于中度，且仅限于某些细胞因子（转化生长因子-β、白细胞介素-1、6和8，但不包括白细胞介素-10、肿瘤坏死因子-α或干扰素-γ）。相比之下，大多数非肝硬化标本显示出有限且低水平的细胞因子基因表达。
这些数据表明转化生长因子-β可能在肝纤维化和炎症中起重要作用。白细胞介素-1β、6、8、肿瘤坏死因子-α和干扰素-γ似乎分别参与了酒精性和丙型肝炎后肝硬化中轻度至重度炎症现象的发病机制。我们的数据表明肿瘤坏死因子-α不参与酒精性肝硬化的肝细胞损伤，并表明至少在丙型肝炎后肝硬化中观察到的水平下，干扰素-γ和白细胞介素-10均无法抵消该疾病中出现的纤维化/炎症过程。
