Andus T, Holstege A
Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Germany.
Acta Gastroenterol Belg. 1994 May-Aug;57(3-4):236-44.
The liver is the largest organ in the body providing a large number of essential functions for the organism. It is the center for the metabolism of nutrients and drugs, and plays a key role in the unspecific immune system by harbouring Kupfer cells, the majority of all macrophages. The liver is the main site for the synthesis of many different metabolites and releases most of the plasma proteins. All these functions of the liver must be coordinated and regulated in response to metabolic changes and minor or major injuries. This is accomplished by metabolites, the autonomous nerve system, the endocrine system and by cytokines, which form a complex network of mediator molecules. Cytokines modulate liver metabolism in many ways. Synthesis of acute phase proteins is regulated by cytokines such as IL-1, IL-6, IL-11, leukemia inhibitory factor, TNF, transforming growth factor beta, epidermal growth factor, and ciliary derived neurotropic factor, which interact synergistically with corticosteroids and insulin. Hepatic lipid metabolism and hepatic carbohydrate metabolism are also regulated by cytokines and by classical hormones. Cytokines play an important role in the pathogenesis of liver diseases and liver fibrosis, which is the common morphological reaction after chronic injury of the liver. An uncontrolled production of extracellular matrix and its impaired degradation destroy the architecture of the liver and its function. Fat-storing cells (Ito cells, lipocytes, perisinusoidal cells) are the major source of extracellular matrix in the liver. They are activated to proliferate or to produce extracellular matrix compounds by cytokines like transforming growth factor beta, and platelet derived growth factor (PDGF). Interferon gamma and alpha inhibit this activation. Modulation of fibrogenesis by these cytokines may be helpful for future treatment of liver fibrosis.
肝脏是人体最大的器官，为机体提供大量重要功能。它是营养物质和药物代谢的中心，通过容纳库普弗细胞（所有巨噬细胞中的大多数）在非特异性免疫系统中发挥关键作用。肝脏是许多不同代谢产物合成的主要场所，并释放大部分血浆蛋白。肝脏的所有这些功能必须根据代谢变化以及轻微或严重损伤进行协调和调节。这是通过代谢产物、自主神经系统、内分泌系统以及细胞因子来完成的，它们形成了一个复杂的介质分子网络。细胞因子以多种方式调节肝脏代谢。急性期蛋白的合成受白细胞介素 -1、白细胞介素 -6、白细胞介素 -11、白血病抑制因子、肿瘤坏死因子、转化生长因子β、表皮生长因子和睫状神经营养因子等细胞因子的调节，这些细胞因子与皮质类固醇和胰岛素协同相互作用。肝脏脂质代谢和肝脏碳水化合物代谢也受细胞因子和经典激素的调节。细胞因子在肝脏疾病和肝纤维化的发病机制中起重要作用，肝纤维化是肝脏慢性损伤后的常见形态学反应。细胞外基质的不受控制产生及其降解受损会破坏肝脏的结构及其功能。贮脂细胞（伊托细胞、脂肪细胞、窦周细胞）是肝脏细胞外基质的主要来源。它们被转化生长因子β和血小板衍生生长因子（PDGF）等细胞因子激活而增殖或产生细胞外基质化合物。干扰素γ和α抑制这种激活。这些细胞因子对纤维生成的调节可能有助于未来肝纤维化的治疗。
