Division of Neonatology/Pulmonary Biology.
Division of Human Genetics, and.
JCI Insight. 2018 Mar 22;3(6):98306. doi: 10.1172/jci.insight.98306.
Neutrophil infiltration of the chorioamnion-decidua tissue at the maternal-fetal interface (chorioamnionitis) is a leading cause of prematurity, fetal inflammation, and perinatal mortality. We induced chorioamnionitis in preterm rhesus macaques by intraamniotic injection of LPS. Here, we show that, during chorioamnionitis, the amnion upregulated phospho-IRAK1-expressed neutrophil chemoattractants CXCL8 and CSF3 in an IL-1-dependent manner. IL-1R blockade decreased chorio-decidua neutrophil accumulation, neutrophil activation, and IL-6 and prostaglandin E2 concentrations in the amniotic fluid. Neutrophils accumulating in the chorio-decidua had increased survival mediated by BCL2A1, and IL-1R blockade also decreased BCL2A1+ chorio-decidua neutrophils. Readouts for inflammation in a cohort of women with preterm delivery and chorioamnionitis were similar to findings in the rhesus macaques. IL-1 is a potential therapeutic target for chorioamnionitis and associated morbidities.
母胎界面的绒毛膜-羊膜组织中的中性粒细胞浸润（绒毛膜羊膜炎）是早产、胎儿炎症和围产儿死亡的主要原因。我们通过羊膜内注射 LPS 诱导早产恒河猴发生绒毛膜羊膜炎。在这里，我们表明，在绒毛膜羊膜炎期间，羊膜以 IL-1 依赖的方式上调磷酸化 IRAK1 表达的中性粒细胞趋化因子 CXCL8 和 CSF3。IL-1R 阻断减少了绒毛膜-蜕膜中的中性粒细胞积累、中性粒细胞激活以及羊水 IL-6 和前列腺素 E2 的浓度。在绒毛膜-蜕膜中积累的中性粒细胞通过 BCL2A1 介导的存活增加，IL-1R 阻断也减少了 BCL2A1+绒毛膜-蜕膜中性粒细胞。在一组患有早产和绒毛膜羊膜炎的妇女的队列中，炎症的检测结果与恒河猴的发现相似。IL-1 是治疗绒毛膜羊膜炎及其相关疾病的潜在靶点。
