University Department of Obstetrics and Gynecology At The Hospital St. Hedwig of The Order of St. John, University of Regensburg, 93049 Regensburg, Germany.
Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci. 2020 Dec 30;22(1):332. doi: 10.3390/ijms22010332.
During pregnancy, infections caused by the gram-positive bacteria (), (), and () are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of , , and collected from pregnant women in preterm labor. Bacterial lysates and, principally, and distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH/TH cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male's vulnerability to preterm birth.
在怀孕期间,革兰氏阳性菌()、()和()引起的感染是导致早产、新生儿早产、脑膜炎或败血症的主要原因。在这里,我们提出了未成熟围生期免疫系统对细菌感染的细胞因子反应是早产和新生儿败血症发病机制的核心因素。我们的目的是通过用从早产孕妇中收集的裂解物刺激新鲜分离的脐血单核细胞(UBMC)来填补对这种细胞因子反应的认识空白。细菌裂解物,主要是和,明显触发了 UBMC 培养物中定量的 11 种炎症、抗炎、TH/TH 细胞因子和趋化因子。趋化因子表现出最强烈的诱导作用。其中,MIP-1β在女性新生儿 UBMC 中的表达进一步增强,而男性新生儿则没有。由于其稳定性和高水平,我们研究了 IL-8 的诊断价值。与胎龄匹配的对照组相比,患有感染的早产儿脐血中 IL-8 显著上调。我们的研究结果提供了关于围产期免疫的新线索,强调了 IL-8 用于及时检测感染的潜在价值,并表明 MIP-1β是性别特异性免疫的早期决定因素,这可能有助于例如男性易患早产。