Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity
Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity
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DOI：
10.1080/14767050500361703
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发表时间：
2005-12-01
影响因子：
1.8
通讯作者：
Kuivaniemi, H
中科院分区：
文献类型：
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作者：
Chaiworapongsa, T;Romero, R;Kuivaniemi, H
目的：巨噬细胞迁移抑制因子（Macrophage migration inhibitory factor， MIF）已成为脓毒性休克的重要介质。在内毒素血症期间使用MIF可增加致死率，而这种细胞因子的中和可防止内毒素休克和与细菌感染相关的死亡。本研究的目的是确定羊膜内感染和人分娩时羊水中MIF浓度是否有变化。研究设计：对以下类别的妇女进行横断面研究：(1)中期妊娠（n = 84）；(2)足月分娩的早产及完整胎膜者（n = 33）；足月分娩的早产（n = 53）及早产合并羊膜内感染者（n = 23）；(3)胎膜早破（PROM）伴（n = 25），无羊膜内感染（n = 26）；(4)胎膜完好，产程（n = 52）和非产程（n = 31）。羊水中MIF浓度测定采用敏感和特异性免疫分析法。在早产和胎膜完整的患者中，也测定了母体血浆中的MIF浓度。免疫组织化学对从不同的早产患者（n = 18）和不（n = 20）的组织学绒毛膜羊膜炎中获得的绒毛膜羊膜进行了检测。采用定量逆转录聚合酶链反应（RT-PCR）技术检测有组织学羊膜炎（n = 13）和无组织学羊膜炎（n = 13）的早产患者羊膜中MIF mRNA的表达。采用参数和非参数、受试者工作特征（ROC）曲线、生存分析和Cox回归模型进行分析。结果：96%（313/327）羊水标本中检测到免疫反应性MIF。足月羊水MIF浓度高于中期（p = 0.004）。羊膜内感染与羊水中位MIF浓度显著升高相关（p分别< 0.001和0.004）。无菌羊水早产患者羊水MIF浓度中位数明显高于足月分娩患者（p = 0.007）。在胎膜完好的早产患者中，生存分析表明，羊水MIF浓度高于302 ng/ml的患者羊膜穿刺术至分娩的中位间隔明显短于低于该临界值的患者（p < 0.001）。人足月分娩与羊水MIF浓度变化无关（p < 0.05）。足月分娩、早产和羊膜感染患者中位母体血浆MIF浓度差异无统计学意义（p < 0.05）。免疫组织化学表明，羊膜上皮细胞中存在MIF蛋白，组织学羊膜炎患者免疫反应性MIF染色细胞的平均百分比高于无此病变的患者（p = 0.03）。同样，组织学羊膜炎患者的绒毛膜中MIF mRNA的平均表达量高于无此病变的患者（p = 0.03）。结论：羊膜内感染和早产，而不是足月分娩，与羊水MIF浓度显著升高相关。在胎膜完好的早产患者中，羊水中MIF浓度升高与羊膜内炎症、组织学绒毛膜羊膜炎和羊膜穿刺术至分娩间隔缩短有关。羊水中的这些变化没有反映在母体血浆中。组织学羊膜炎患者羊膜中MIF蛋白和mRNA表达增加。
Objective: Macrophage migration inhibitory factor (MIF) has emerged as an important mediator of septic shock. The administration of MIF increases lethality during endotoxemia, whereas neutralization of this cytokine prevents endotoxic shock and death associated with bacterial infection. The objective of this study was to determine whether there is a change in the amniotic fluid concentration of MIF in intra-amniotic infection and human parturition.Study design: A cross-sectional study was conducted in women in the following categories: (1) mid-trimester (n = 84); (2) preterm labor and intact membranes who delivered at term (n = 33), who delivered preterm (n = 53) and preterm labor with intra-amniotic infection (n = 23); (3) preterm premature rupture of membranes (PROM) with (n = 25) and without intraamniotic infection (n = 26); and (4) term with intact membranes, in labor (n = 52) and not in labor (n = 31). MIF concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. MIF concentrations in maternal plasma were also determined in patients with preterm labor and intact membranes. Immunohistochemistry was conducted in chorioamniotic membranes obtained from a different set of patients presenting with preterm labor with (n = 18) and without (n = 20) histologic chorioamnionitis. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to measure MIF mRNA expression in chorioamniotic membranes of patients with preterm labor with (n = 13) and without (n = 13) histologic chorioamnionitis. Parametric and non-parametric, receiver-operating characteristic (ROC) curve, survival analysis, and Cox regression model were used for analysis.Results: Immunoreactive MIF was detectable in 96% (313/327) of amniotic fluid samples. The concentration of amniotic fluid MIF at term was higher than that in the mid-trimester (p = 0.004). Intra-amniotic infection in women with preterm labor and preterm PROM was associated with a significant increase in median amniotic fluid MIF concentration (p < 0.001 and 0.004, respectively). Patients with preterm labor with sterile amniotic fluid who delivered preterm had a significantly higher median amniotic fluid MIF concentration than those who delivered at term (p = 0.007). Among patients with preterm labor with intact membranes, survival analysis indicated that the median amniocentesis-to-delivery interval was significantly shorter in patients whose amniotic fluid concentrations of MIF were above 302 ng/ml than those below this cutoff value (p < 0.001). Human parturition at term was not associated with changes in the amniotic fluid MIF concentrations (p > 0.05). There was no significant difference in median maternal plasma MIF concentrations among patients with preterm labor and intact membranes who delivered at term, those who delivered preterm, and those who had intra-amniotic infection (p > 0.05 for all comparisons). Immunohistochemistry demonstrated that MIF protein was present in amniotic epithelial cells, and the mean percentage of immunoreactive MIF-staining cells was higher in patients with histologic chorioamnionitis than in those without this lesion (p = 0.03). Similarly, the mean MIF mRNA expression was higher in chorioamniotic membranes obtained from patients with histologic chorioamnionitis than in those without this lesion (p = 0.03).Conclusions: Intra-amniotic infection and preterm parturition, but not term parturition, are associated with a significant increase in amniotic fluid MIF concentrations. Among patients with preterm labor with intact membranes, elevated amniotic fluid concentrations of MIF are associated with intra-amniotic inflammation, histologic chorioamnionitis, and shorter amniocentesis-to-delivery interval. These changes in amniotic fluid were not reflected in maternal plasma. An increased expression of MIF protein and mRNA in chorioamniotic membranes was observed in patients with histologic choricamnionitis.