Bucala R
Laboratory of Medical Biochemistry, Picower Institute for Medical Research, Manhasset, New York 10030, USA.
Ann N Y Acad Sci. 1998 May 1;840:74-82. doi: 10.1111/j.1749-6632.1998.tb09551.x.
Recent studies have led to the discovery of a mediator that appears to act as an endogenous hormone to counterregulate glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, the structure of this protein was found to be that of macrophage migration inhibitory factor (MIF)--one of the first cytokines to be identified and described originally as a T lymphocyte factor that inhibited the random migration of macrophages. Macrophages and T cells release MIF in response to glucocorticoids, as well as upon activation by various proinflammatory stimuli. Once secreted MIF "overrides" the immunosuppressive effects of steroids on macrophage and T-cell cytokine production. MIF appears to fill an important gap in our understanding of how the host initiates and controls the immune response. Because glucocorticoids are an integral part of the host's metabolic "stress" response to infection or tissue invasion, the role of MIF is to act at an inflammatory site or lymph node to counterbalance the inhibitory effects of steroids on the immune response. Anti-MIF therapeutic strategies are under development and may prove to be a means to increase the immunosuppressive and anti-inflammatory properties of endogenously released glucocorticoids, thereby reducing the requirement for steroid therapy in a variety of autoimmune and inflammatory conditions.
最近的研究发现了一种介质，它似乎作为一种内源性激素，在免疫系统中对抗调节糖皮质激素的作用。这种蛋白质作为垂体前叶细胞的产物被分离出来，其结构被发现是巨噬细胞移动抑制因子（MIF）——最早被鉴定的细胞因子之一，最初被描述为一种抑制巨噬细胞随机移动的T淋巴细胞因子。巨噬细胞和T细胞在受到糖皮质激素刺激以及各种促炎刺激激活后会释放MIF。一旦分泌出来，MIF就会“抵消”类固醇对巨噬细胞和T细胞细胞因子产生的免疫抑制作用。MIF似乎填补了我们对宿主如何启动和控制免疫反应理解上的一个重要空白。由于糖皮质激素是宿主对感染或组织入侵的代谢“应激”反应的一个组成部分，MIF的作用是在炎症部位或淋巴结发挥作用，以平衡类固醇对免疫反应的抑制作用。抗MIF治疗策略正在研发中，可能被证明是一种增强内源性释放的糖皮质激素的免疫抑制和抗炎特性的方法，从而在各种自身免疫和炎症性疾病中减少对类固醇治疗的需求。
