Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis
Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis
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DOI：
10.1086/514344
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发表时间：
2007-05-15
影响因子：
11.8
通讯作者：
Calandra, Thierry
中科院分区：
文献类型：
--
作者：
Emonts, Marieke;Sweep, Fred C. G. J.;Calandra, Thierry
背景。确定新的治疗靶点仍然是改善严重脓毒症和感染性休克相关发病率和死亡率的迫切目标。巨噬细胞迁移抑制因子（MIF）是一种促炎细胞因子和糖皮质激素的反调节剂，最近已成为先天免疫和实验性脓毒症的关键介质，是治疗脓毒症的一个有吸引力的新靶点。在 2 个临床试验队列中测量了 145 名儿童和成人患者的 MIF 循环浓度，这些患者主要由脑膜炎奈瑟菌或其他革兰氏阴性菌感染引起严重脓毒症或脓毒性休克，以研究脓毒症期间 MIF 的动力学，分析 MIF 与脓毒症或应激激素（促肾上腺皮质激素和皮质醇）的其他介质之间的相互作用，并确定 MIF 是否与患者预后相关。结果。 96% 患有严重败血症或败血性休克的儿童和成人的 MIF 循环浓度显着升高，并且在数天内仍保持升高状态。 MIF 水平与脓毒症严重程度评分、休克的存在、弥散性血管内凝血、尿量、血液 pH 值以及乳酸和细胞因子水平相关。高水平的 MIF 与快速致命的结果相关。此外，在脑膜炎球菌脓毒症中，MIF浓度与促肾上腺皮质激素水平呈正相关，与皮质醇水平和皮质醇：促肾上腺皮质激素比率呈负相关，表明肾上腺对脓毒症有不适当的反应。结论。 MIF 在患有革兰氏阴性败血症的儿童和成人中显着且持续上调，并且与疾病严重程度参数、脑膜炎球菌败血症中的垂体肾上腺功能失调以及过早死亡相关。
Background. Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently emerged as a critical mediator of innate immunity and experimental sepsis, and it is an attractive new target for the treatment of sepsis.Methods. Circulating concentrations of MIF were measured in 2 clinical trial cohorts of 145 pediatric and adult patients who had severe sepsis or septic shock caused predominantly by infection with Neisseria meningitidis or other gram-negative bacteria, to study the kinetics of MIF during sepsis, to analyze the interplay between MIF and other mediators of sepsis or stress hormones (adrenocorticotropic hormone and cortisol), and to determine whether MIF is associated with patient outcome.Results. Circulating concentrations of MIF were markedly elevated in 96% of children and adults who had severe sepsis or septic shock, and they remained elevated for several days. MIF levels were correlated with sepsis severity scores, presence of shock, disseminated intravascular coagulation, urine output, blood pH, and lactate and cytokine levels. High levels of MIF were associated with a rapidly fatal outcome. Moreover, in meningococcal sepsis, concentrations of MIF were positively correlated with adrenocorticotropic hormone levels and negatively correlated with cortisol levels and the cortisol: adrenocorticotropic hormone ratio, suggesting an inappropriate adrenal response to sepsis.Conclusions. MIF is markedly and persistently up-regulated in children and adults with gram-negative sepsis and is associated with parameters of disease severity, with dysregulated pituitary-adrenal function in meningococcal sepsis, and with early death.