Hammerich Linda, Tacke Frank
Department of Medicine III, University Hospital Aachen, Aachen, Germany.
Clin Exp Gastroenterol. 2014 Sep 1;7:297-306. doi: 10.2147/CEG.S43737. eCollection 2014.
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.
白细胞介素是一类免疫调节细胞因子，即小型细胞间信号蛋白，在免疫反应调节中起关键作用。它们在炎症反应期间由多种细胞类型大量产生，细胞因子的平衡决定免疫反应的结果。因此，细胞因子被视为治疗肝病患者的有趣治疗靶点。小鼠模型为细胞因子功能的体内研究提供了良好工具，因为人和小鼠的细胞因子有许多同源性。复杂的小鼠模型，无论是模拟不同的病理状况，还是针对肝脏甚至不同细胞区室中的细胞因子和细胞因子信号通路，都为白细胞介素在肝脏炎症中的不同功能提供了深入见解。在慢性肝病中，白细胞介素可能具有促炎和抗炎功能，有些白细胞介素甚至兼具这两种功能，这取决于炎症刺激、产生细胞和反应细胞类型。例如，IL-17通过激活肝星状细胞促进肝纤维化，并通过募集髓源性抑制细胞促进肝癌的发展。另一方面，IL-22可防止肝纤维化或脂肪性肝炎的发展。在传染病模型中，IL-12平衡辅助性T细胞（Th）1和Th2细胞反应。IL-13和IL-33这两种与Th2细胞和固有淋巴细胞相关的细胞因子，促进肝脏的纤维化反应。IL-10是典型的抗炎白细胞介素，在慢性肝损伤和纤维化过程中具有组织保护功能。尽管IL-6信号在诱导肝脏急性期反应中起关键作用，但在纤维化进展过程中具有保护作用，但会促进肝细胞癌。对小鼠的实验研究有助于确定特定细胞因子对慢性肝病结局的确切影响，并确定有用的治疗靶点。
