Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria
Macrophage migration inhibitory factor (MIF) modulates innate immune responses induced by endotoxin and Gram-negative bacteria
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DOI：
10.1177/09680519010070061101
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Calandra, T
中科院分区：
文献类型：
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作者：
Roger, T;Glauser, MP;Calandra, T
MIF 于 20 世纪 60 年代初作为 T 细胞细胞因子被发现，现已成为先天免疫系统的重要介质。最近发现，大量细胞（包括单核细胞/巨噬细胞、T 细胞、B 细胞、内分泌细胞和上皮细胞）响应感染和应激而释放 MIF。细菌、微生物毒素和细胞因子已被证明是巨噬细胞分泌 MIF 的强大诱导剂。 MIF 刺激免疫细胞表达促炎介质，并具有抵消糖皮质激素的抗炎和免疫抑制作用的作用。与 TNF 和 IL-1 一样，MIF 在宿主对感染的反应中发挥着重要作用。研究发现，当与 LPS 或大肠杆菌共同注射小鼠时，重组 MIF 会加剧致命性内毒素血症或细菌性败血症。相反，MIF 基因敲除小鼠或用抗 MIF 抗体治疗的小鼠可以免受 LPS、葡萄球菌外毒素或细菌性腹膜炎引起的休克，即使在感染发作后开始抗 MIF 治疗也是如此。鉴于 MIF 在针对微生物病原体的先天免疫反应和炎症反应调节中发挥的核心作用，MIF 产生的药理调节或 MIF 活性的中和可能具有广泛的临床应用，并可能为严重脓毒症或感染性休克患者的治疗提供新的治疗选择。
Discovered in the early 1960s as a T-cell cytokine, MIF has emerged to be an important mediator of the innate immune system. MIF was identified recently to be released by a vast array of cells, including monocytes/macrophages, T-cells, B-cells, endocrine cells and epithelial cells in response to infection and stress. Bacteria, microbial toxins and cytokines have been shown to be powerful inducers of MIF secretion by macrophages. MIF stimulates the expression of pro-inflammatory mediators by immune cells and functions to counterbalance the anti-inflammatory and immunosuppressive effects of glucocorticoids. Like TNF and IL-1, MIF plays an important role in host responses to infection. Recombinant MIF was found to exacerbate lethal endotoxemia or bacterial sepsis when co-injected with LPS or Escherichia coli in mice. Conversely, MIF knockout mice or mice treated with anti-MIF antibodies were protected from shock, induced by LPS, staphylococcal exotoxins or bacterial peritonitis, even when anti-MIF therapy was started after the onset of infection. Given the central role played by MIF in innate immune responses against microbial pathogens and in the regulation of inflammatory responses, pharmacological modulation of MIF production or neutralization of MIF activity could have broad clinical applications and may offer new treatment options for the management of patients with severe sepsis or septic shock.