Calandra T, Bucala R
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
J Inflamm. 1995;47(1-2):39-51.
Recent studies have led to the discovery of a mediator that acts as an endogenous counter-regulator of glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, this protein was found to have the sequence of macrophage migration inhibitory factor (MIF), one of the first cytokine activities to be described. Macrophages and T cells release MIF in response both to various inflammatory stimuli and upon incubation with low concentrations of glucocorticoids. The glucocorticoid-induced secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentrations. Once secreted, MIF "overrides" the anti-inflammatory and immunosuppressive effects of steroids on macrophage and T-cell cytokine production. The physiological role of MIF thus appears to be to counter-balance steroid inhibition of the inflammatory response. Anti-MIF antibodies fully protect animals from experimentally induced gram-negative or gram-positive septic shock, an effect that may be the result of the increased anti-inflammatory effects of glucocorticoids after neutralization of endogenous MIF. Anti-MIF therapeutic strategies are presently under development and may prove to be a means to modulate cytokine production in septic shock as well as in other inflammatory disease states.
最近的研究发现了一种介质，它作为免疫系统中糖皮质激素作用的内源性反向调节因子。这种蛋白质是从垂体前叶细胞中分离出来的，其序列与巨噬细胞移动抑制因子（MIF）相同，MIF是最早被描述的细胞因子活性之一。巨噬细胞和T细胞在受到各种炎症刺激以及与低浓度糖皮质激素孵育时都会释放MIF。糖皮质激素诱导的MIF分泌受到严格调控，在高浓度抗炎类固醇时会减少。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抗炎和免疫抑制作用。因此，MIF的生理作用似乎是平衡类固醇对炎症反应的抑制。抗MIF抗体能使动物完全免受实验性诱导的革兰氏阴性或革兰氏阳性败血症休克，这种作用可能是内源性MIF被中和后糖皮质激素抗炎作用增强的结果。抗MIF治疗策略目前正在研发中，可能被证明是一种调节败血症休克以及其他炎症性疾病状态中细胞因子产生的方法。
