MIF IS A PITUITARY-DERIVED CYTOKINE THAT POTENTIATES LETHAL ENDOTOXEMIA
MIF IS A PITUITARY-DERIVED CYTOKINE THAT POTENTIATES LETHAL ENDOTOXEMIA
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DOI：
10.1038/365756a0
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发表时间：
1993-10-21
期刊：
影响因子：
64.8
通讯作者：
BUCALA, R
中科院分区：
文献类型：
--
作者：
BERNHAGEN, J;CALANDRA, T;BUCALA, R
细胞因子在导致败血性休克的通常致命的级联事件中至关重要1 -3。在控制炎症反应中可能很重要的一个调节系统是神经内分泌轴。例如，脑垂体处于整合中枢和外周刺激的理想位置4，并启动伴随宿主应激反应的全身性糖皮质激素的增加6 -8。为了进一步评估垂体对全身炎症过程的贡献，我们研究了细菌脂多糖（LPS）刺激后培养的垂体细胞和整个垂体的分泌特征。在这里，我们确定巨噬细胞移动抑制因子（MIF）9-11作为一个主要的分泌蛋白释放的垂体前叶细胞在响应LPS刺激。对照、垂体切除和T细胞缺陷（裸）小鼠的血清分析表明，垂体衍生的MIF有助于内毒素血症急性期后存在的循环MIF。当与LPS共注射时，重组鼠MIF大大增强致死性，并且抗MIF抗体赋予针对致死性内毒素血症的完全保护。我们的结论是，MIF起着核心作用的毒性反应，内毒素血症和可能的特异性休克。
CYTOKINES are critical in the often fatal cascade of events that cause septic shock1-3. One regulatory system that is likely to be important in controlling inflammatory responses is the neuroendocrine axis. The pituitary, for example, is ideally situated to integrate central and peripheral stimuli4, and initiates the increase in systemic glucocorticoids that accompanies host stress responses6-8. To assess further the contribution of the pituitary to systemic inflammatory processes, we examined the secretory profile of cultured pituitary cells and whole pituitaries in vivo after stimulation with bacterial lipopolysaccharide (LPS). Here we identify macrophage migration inhibitory factor (MIF)9-11 as a major secreted protein released by anterior pituitary cells in response to LPS stimulation. Serum analysis of control, hypophysectomized and T-cell-deficient (nude) mice suggests that pituitary-derived MIF contributes to circulating MIF present in the post-acute phase of endotoxaemia. Recombinant murine MIF greatly enhances lethality when co-injected with LPS and anti-MIF antibody confers full protection against lethal endotoxaemia. We conclude that MIF plays a central role in the toxic response to endotoxaemia and possibly spetic shock.