The cytokine network in the pathogenesis of systemic lupus erythematosus and possible therapeutic implications.
The cytokine network in the pathogenesis of systemic lupus erythematosus and possible therapeutic implications.
复制标题
系统性红斑狼疮发病机制中的细胞因子网络及其可能的治疗意义。
DOI：
10.1007/bf00197516
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Jacob,CO
中科院分区：
文献类型：
--
作者：
Horwitz,DA;Jacob,CO
系统性红斑狼疮（SLE）被认为是人类自身免疫性疾病的原型。它是一种全身性自身免疫性疾病，以多系统器官受累和抗核、胞质和细胞表面抗原的自身抗体为特征。对这些自身抗原耐受性的破坏机制尚不清楚。T细胞、B细胞和抗原呈递细胞的减少导致免疫失调，尤其是在活动性疾病患者中。存在多克隆B细胞活化和自身抗体形成的B细胞过度活跃。相比之下，细胞免疫力下降，T细胞和自然杀伤（NK）细胞效应子功能受损，导致宿主防御力下降[50]。多年来，研究人员一直在寻找在发病机制中重要的T细胞原发性异常。然而，大多数T细胞异常似乎反映了疾病引起的调节异常。为了解释SLE免疫失调的机制，细胞因子受到越来越多的关注。细胞因子是由多种细胞产生的蛋白质样低分子量蛋白质，对免疫系统具有深远的影响。细胞因子介导各种各样的功能并发挥显著不同的作用。已知细胞因子的数量持续增加，并且已知一些细胞因子具有冗余的功能特性。今天的一个关键问题不仅是哪些细胞因子可能参与免疫反应或疾病的病理生理学，而且这些细胞因子何时起作用以及它们的许多活性中哪些与体内相关。复杂性源于这样的事实，即给定细胞因子的表达总是受到形成细胞因子级联网络的其他细胞因子的影响。这种级联反应可能代表细胞程序化生长、分化和功能中细胞因子作用的重要特征。此外，复杂性还源自大范围的蜂窝通信。
Systemic lupus erythematosus (SLE) is considered to be the prototype of human autoimmune diseases. It is a disorder of generalized autoimmunity characterized by multisystem organ involvement and autoantibodies against nuclear, cytoplasmic, and cell surface antigens. The mechanisms responsible for the breakdown of tolerance against these self antigens are unknown. Abnormalities of T cells, B cells and antigenpresenting cells result in immune dysregulation, especially in patients with active disease. There is B cell hyperactivity with polyclonal B cell activation and autoantibody formation. By contrast, there is decreased cellular immunity with impaired T cell and natural killer (NK) cell effector functions leading to decreased host defense [50]. For many years investigators have searched for primary abnormalities of T cells which are important in pathogenesis. Most of the T cell abnormalities, however, appear to reflect dysregulation as a consequence of the disease. To explain the mechanisms responsible for immune dysregulation in SLE, cytokines have received increasing attention. Cytokines are hormone-like low molecular weight proteins, produced by a wide variety of cells, that have profound effects on the immune system. Cytokines mediate a large variety of functions and exert remarkably diverse effects. The number of known cytokines continues to increase and some have been known to have redundant functional properties. A key question today is not only which cytokines are potentially involved in the pathophysiology of an immune response or disease, but when do these cytokines function and which of their many activities are relevant in vivo. Complexity derives from the fact that the expression of a given cytokine is invariably influenced by other cytokines forming networks of cytokine cascades. Such cascades may represent important features of cytokine action in the programmed growth, differentiation and function of cells. Furthermore, complexity also derives from the large range of cellular