Calandra T, Bucala R
Picower Institute for Medical Research, Laboratory of Medical Biochemistry, Manhasset, NY 11030, USA.
Crit Rev Immunol. 1997;17(1):77-88. doi: 10.1615/critrevimmunol.v17.i1.30.
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 TNF alpha, IL-1 beta, 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-gamma 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.
巨噬细胞移动抑制因子（MIF）最初被描述为一种抑制巨噬细胞随机迁移的T淋巴细胞衍生因子，在近30年里一直是一种神秘的细胞因子。近年来，MIF作为垂体前叶产物的发现以及生物活性重组MIF蛋白的克隆和表达，使其在体内的关键生物学作用得以明确。MIF具有从受糖皮质激素刺激的巨噬细胞和T淋巴细胞中释放的独特特性。一旦释放，MIF可克服糖皮质激素对体外脂多糖刺激的单核细胞产生肿瘤坏死因子α、白细胞介素-1β、白细胞介素-6和白细胞介素-8的抑制作用，并在体内抑制类固醇对致死性内毒素血症的保护作用。MIF还通过恢复白细胞介素-2和γ干扰素的产生，在体外拮抗糖皮质激素对T细胞增殖的抑制作用。这一发现确定了MIF在免疫系统中的关键作用，并填补了我们对炎症和免疫反应控制理解上的一个重要空白。长期以来，糖皮质激素一直被认为是对感染或组织入侵应激反应的一个组成部分，并用于调节炎症和免疫反应。MIF是第一个被确定的能够对抗糖皮质激素抑制作用的介质，因此在宿主对炎症和免疫的控制中起着关键作用。
