Maltby J, Wright S, Bird G, Sheron N
Department of Medicine, University of Southampton, Southampton General Hospital, UK.
Hepatology. 1996 Nov;24(5):1156-60. doi: 10.1053/jhep.1996.v24.pm0008903391.
Alcoholic hepatitis is characterized by parenchymal neutrophil infiltration. Hepatic synthesis of the neutrophil chemokine interleukin-8 (IL-8) is highly elevated in alcoholic hepatitis and levels correlate with the degree of neutrophil infiltration. The aim of this study was to further determine the spectrum of synthesis of chemokines in liver tissue from patients with alcoholic liver disease and a range of disease control subjects. Subjects were composed of 24 patients with alcoholic liver disease of whom 15 had histopathological evidence of alcoholic hepatitis (10 cirrhotic) and 9 no evidence of alcoholic hepatitis (5 cirrhotic); other controls included; normal liver (n = 6), viral hepatitis (n = 16), primary biliary cirrhosis (n = 5), acute liver failure (n = 4), and miscellaneous liver disease (n = 13). Levels of the C-X-C neutrophil chemokine GRO alpha and the mononuclear cell C-C chemokines: macrophage inflammatory protein 1 alpha, macrophage chemotactic protein 1 and RANTES, were determined by ELISA in liver homogenates. Levels of the neutrophil chemokine GRO alpha were specifically elevated (mean 46 pg/mg, compared with normal liver 11 pg/mg) in patients with alcoholic hepatitis. GRO alpha levels correlated with IL-8 levels and were higher in patients with alcoholic liver disease and parenchymal neutrophil infiltration. Hepatic RANTES was elevated in diseased liver, with the highest levels found in viral hepatitis (mean 117 pg/mg, compared with 24 pg/mg in normal liver). No significant changes in hepatic levels of macrophage inflammatory protein 1 alpha (MIP-1 alpha) or macrophage chemotactic protein 1 (MCP-1) were found. These data provide further supportive evidence that parenchymal neutrophil infiltration in alcoholic hepatitis may be determined by selective upregulation of C-X-C chemokine synthesis.
酒精性肝炎的特征是实质内中性粒细胞浸润。在酒精性肝炎中，肝脏合成的中性粒细胞趋化因子白细胞介素-8（IL-8）显著升高，其水平与中性粒细胞浸润程度相关。本研究的目的是进一步确定酒精性肝病患者及一系列疾病对照受试者肝脏组织中趋化因子的合成谱。受试者包括24例酒精性肝病患者，其中15例有酒精性肝炎的组织病理学证据（10例为肝硬化），9例无酒精性肝炎证据（5例为肝硬化）；其他对照包括：正常肝脏（n = 6）、病毒性肝炎（n = 16）、原发性胆汁性肝硬化（n = 5）、急性肝衰竭（n = 4）和其他肝病（n = 13）。通过酶联免疫吸附测定法（ELISA）测定肝脏匀浆中C-X-C中性粒细胞趋化因子GROα以及单核细胞C-C趋化因子：巨噬细胞炎性蛋白1α、巨噬细胞趋化蛋白1和调节激活正常T细胞表达和分泌因子（RANTES）的水平。酒精性肝炎患者的中性粒细胞趋化因子GROα水平显著升高（平均46 pg/mg，正常肝脏为11 pg/mg）。GROα水平与IL-8水平相关，在有实质内中性粒细胞浸润的酒精性肝病患者中更高。肝脏RANTES在病变肝脏中升高，在病毒性肝炎中水平最高（平均117 pg/mg，正常肝脏为24 pg/mg）。未发现肝脏中巨噬细胞炎性蛋白1α（MIP-1α）或巨噬细胞趋化蛋白1（MCP-1）水平有显著变化。这些数据提供了进一步的支持性证据，表明酒精性肝炎中实质内中性粒细胞浸润可能由C-X-C趋化因子合成的选择性上调所决定。
