Interleukins in chronic liver disease: lessons learned from experimental mouse models.
Interleukins in chronic liver disease: lessons learned from experimental mouse models.
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DOI：
10.2147/ceg.s43737
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发表时间：
2014
影响因子：
2.4
通讯作者：
Tacke F
中科院分区：
文献类型：
--
作者：
Hammerich L;Tacke F
白细胞介素代表一类免疫调节性细胞因子，小的细胞间信号传导蛋白，其关键地参与免疫应答的调节。它们在炎症反应期间由各种细胞类型大量产生，并且细胞因子的平衡决定免疫应答的结果。因此，细胞因子被认为是治疗肝病患者的有趣的治疗靶点。小鼠模型为细胞因子功能的体内研究提供了良好的工具，因为人和小鼠细胞因子具有许多同源性。复杂的小鼠模型，无论是模仿不同的病理条件或靶向细胞因子和干扰素信号通路在肝脏中，甚至在不同的细胞隔室提供了巨大的洞察白细胞介素在肝脏炎症过程中的不同功能。白细胞介素在慢性肝病中可能具有促炎和抗炎功能，某些白细胞介素甚至两者兼有，这取决于炎症刺激、产生和应答细胞类型。例如，IL-17通过激活肝星状细胞促进肝纤维化，并通过募集骨髓源性抑制细胞促进肝癌的发展。另一方面，IL-22可防止纤维化或脂肪性肝炎的发展。IL-12平衡感染性疾病模型中的辅助性T（Th）-1和Th 2细胞应答。IL-13和IL-33，两种与Th 2细胞和先天淋巴细胞相关的细胞因子，促进肝脏中的纤维化反应。IL-10是典型的抗炎白细胞介素，在慢性肝损伤和肝纤维化过程中具有组织保护功能。尽管IL-6信号传导在诱导肝脏急性期反应中起关键作用，但在纤维化进展期间具有保护作用，但促进肝细胞癌。小鼠实验研究有助于确定特定细胞因子对慢性肝病结果的确切影响，并确定有用的治疗靶点。
Interleukins represent a class of immunomodulatory cytokines, small intercellular signaling proteins, that are critically involved in the regulation of immune responses. They are produced in large amounts by various cell types during inflammatory reactions, and the balance of cytokines determines the outcome of an immune response. Therefore, cytokines are regarded as interesting therapeutic targets for the treatment of patients with liver diseases. Mouse models provide a good tool for in vivo studies on cytokine function, as human and mouse cytokines share many homologies. Sophisticated mouse models either mimicking distinct pathological conditions or targeting cytokines and cytokine-signaling pathways in the liver or even in distinct cellular compartments have provided enormous insight into the different functions of interleukins during hepatic inflammation. Interleukins may have pro- as well as anti-inflammatory functions in chronic liver diseases, some interleukins even both, dependent on the inflammatory stimulus, the producing and the responding cell type. IL-17, for example, promotes hepatic fibrogenesis through activation of hepatic stellate cells and facilitates development of liver cancer through recruitment of myeloid-derived suppressor cells. IL-22, on the other hand, protects from development of fibrosis or steatohepatitis. IL-12 balances T-helper (Th)-1 and Th2 cell responses in infectious disease models. IL-13 and IL-33, two cytokines related to Th2 cells and innate lymphoid cells, promote fibrotic responses in the liver. IL-10 is the prototypic anti-inflammatory interleukin with tissue-protective functions during chronic liver injury and fibrogenesis. Despite its critical role for inducing the acute-phase response in the liver, IL-6 signaling is protective during fibrosis progression, but promotes hepatocellular carcinoma. Experimental studies in mice help to define the exact influence of a specific cytokine on the outcome of chronic liver diseases and to identify useful therapeutic targets.