Mechanisms of Immune-Mediated Liver Injury
Mechanisms of Immune-Mediated Liver Injury
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DOI：
10.1093/toxsci/kfq009
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发表时间：
2010-06-01
影响因子：
3.8
通讯作者：
Jaeschke, Hartmut
中科院分区：
文献类型：
--
作者：
Adams, David H.;Ju, Cynthia;Jaeschke, Hartmut
肝脏炎症是包括药物性肝毒性在内的多种肝脏疾病的常见表现。炎性表型可归因于枯否细胞、单核细胞、中性粒细胞和淋巴细胞产生的先天免疫应答。适应性免疫系统也受到先天免疫反应的影响，导致肝损伤。本文综述了近年来免疫介导的肝毒性机制及其在药物性肝损伤中的应用。淋巴细胞，巨噬细胞和中性粒细胞的激活的基本机制和他们独特的招募机制进入肝脏血管系统进行了讨论。特别是，粘附分子和各种炎症介质在这一过程中的作用进行了探讨。此外，作者描述了这些炎性细胞对肝细胞损伤的机制，并严格评价了每种细胞类型对预测性和特异质药物诱导的肝损伤的功能意义。预计我们对肝损伤免疫机制的理解的持续进步将导致更早地检测正在开发的药物的肝毒性潜力，并更早地识别具有预测性和特异质药物毒性风险的易感个体。
Hepatic inflammation is a common finding during a variety of liver diseases including drug-induced liver toxicity. The inflammatory phenotype can be attributed to the innate immune response generated by Kupffer cells, monocytes, neutrophils, and lymphocytes. The adaptive immune system is also influenced by the innate immune response leading to liver damage. This review summarizes recent advances in specific mechanisms of immune-mediated hepatotoxicity and its application to drug-induced liver injury. Basic mechanisms of activation of lymphocytes, macrophages, and neutrophils and their unique mechanisms of recruitment into the liver vasculature are discussed. In particular, the role of adhesion molecules and various inflammatory mediators in this process are explored. In addition, the authors describe mechanisms of liver cell damage by these inflammatory cells and critically evaluate the functional significance of each cell type for predictive and idiosyncratic drug-induced liver injury. It is expected that continued advances in our understanding of immune mechanisms of liver injury will lead to an earlier detection of the hepatotoxic potential of drugs under development and to an earlier identification of susceptible individuals at risk for predictive and idiosyncratic drug toxicities.