Originally described as a T lymphocyte-derived factor that inhibited the random migration of macrophages, the protein known as macrophage migration inhibitory factor (MIF) was an enigmatic cytokine for almost 3 decades. In recent years, the discovery of MIF as a product of the anterior pituitary gland and the cloning and expression of bioactive, recombinant MIF protein have led to the definition of its critical biological role in vivo. MIF has the unique property of being released from macrophages and T lymphocytes that have been stimulated by glucocorticoids. Once released, MIF overcomes the inhibitory effects of glucocorticoids on TNFα, IL-1β, IL-6, and IL-8 production by LPS-stimulated monocytes in vitro and suppresses the protective effects of steroids against lethal endotoxemia in vivo. MIF also antagonizes glucocorticoid inhibition of T-cell proliferation in vitro by restoring IL-2 and IFN-γ production. This observation has identified a pivotal role for MIF within the immune system and fills an important gap in our understanding of the control of inflammatory and immune responses. Glucocorticoids have long been considered to be an integral component of the stress response to infection or tissue invasion and serve to modulate inflammatory and immune responses. MIF is the first mediator to be identified that can counter-regulate the inhibitory effects of glucocorticoids and thus plays a critical role in the host control of inflammation and immunity.

中文翻译：

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巨噬细胞迁移抑制因子（MIF）：免疫系统中的糖皮质激素抗调节剂。

最初被描述为抑制巨噬细胞随机迁移的T淋巴细胞衍生因子，被称为巨噬细胞迁移抑制因子（MIF）的蛋白质在长达近30年的时间里都是一个神秘的细胞因子。近年来，作为垂体前叶产物的MIF的发现以及具有生物活性的重组MIF蛋白的克隆和表达，导致了其在体内关键生物学作用的定义。MIF具有从糖皮质激素刺激的巨噬细胞和T淋巴细胞释放的独特特性。释放后，MIF克服了糖皮质激素对LPS刺激的单核细胞在体外对TNFα，IL-1β，IL-6和IL-8产生的抑制作用，并抑制了类固醇在体内对致死性内毒素血症的保护作用。MIF还通过恢复IL-2和IFN-γ的产生来拮抗糖皮质激素在体外对T细胞增殖的抑制作用。这项发现已经确定了MIF在免疫系统中的关键作用，填补了我们对炎症和免疫反应控制的认识上的重要空白。长期以来，糖皮质激素一直被认为是对感染或组织入侵的应激反应不可或缺的组成部分，可调节炎症和免疫反应。MIF是第一个被发现能够介导调节糖皮质激素抑制作用的介体，因此在宿主的炎症和免疫控制中起着至关重要的作用。这项发现已经确定了MIF在免疫系统中的关键作用，填补了我们对炎症和免疫反应控制的认识上的重要空白。长期以来，糖皮质激素一直被认为是对感染或组织入侵的应激反应不可或缺的组成部分，可调节炎症和免疫反应。MIF是第一个被发现能够介导调节糖皮质激素抑制作用的介体，因此在宿主的炎症和免疫控制中起着至关重要的作用。这项发现已经确定了MIF在免疫系统中的关键作用，填补了我们对炎症和免疫反应控制的认识上的重要空白。长期以来，糖皮质激素一直被认为是对感染或组织入侵的应激反应不可或缺的组成部分，可调节炎症和免疫反应。MIF是第一个被发现能够介导调节糖皮质激素抑制作用的介体，因此在宿主的炎症和免疫控制中起着至关重要的作用。