Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Pediatr Res. 2023 Feb;93(3):675-681. doi: 10.1038/s41390-022-02147-z. Epub 2022 Jun 11.
The source and clearance of cytokines in the fetal circulation in term pregnancies complicated by chorioamnionitis remains unclear as are the contributions of placental transport, synthesis, and clearance. The objectives of the study were to determine (1) fetal and/or placental contributions to synthesis and/or clearance of inflammatory and anti-inflammatory cytokines in term pregnancies complicated by chorioamnionitis and (2) whether this differs in pregnancies further complicated by fetal hypoxia.
Prospective cohort study of pregnancies >37 weeks gestational age that included: Group 1, uncomplicated cesarean delivery without labor (n = 20); Group 2, uncomplicated vaginal delivery (n = 30); Group 3, pregnancies complicated by chorioamnionitis (n = 10); Group 4, complicated by chorioamnionitis + fetal hypoxia (n = 10). Umbilical arterial (UmA) and venous (UmV) blood were assayed for IL-1β, IL-2, IL-6, IL-8, TNFα, and IL-10.
IL-6 and IL-8 were below assay detection in UmA and UmV blood in Group 1 and increased in Group 2 (P < 0.01), UmA»UmV (P < 0.01). Their concentrations increased further in Groups 3 and 4 (P = 0.003), UmA»UmV. Placental clearance was concentration dependent that approaches saturation in the presence of chorioamnionitis.
Marked increases in fetal synthesis of IL-6 and IL-8 occur in chorioamnionitis. Synthesis increase further when complicated by fetal hypoxia. Cytokine removal occurs via placental concentration-dependent mechanisms, potentially contributing to adverse fetal effects.
The source and role of the placenta in synthesis and/or clearance of inflammatory mediators in term pregnancies complicated by clinical chorioamnionitis are unclear; however, conventional wisdom suggests the placenta is their source. This is the first study demonstrating that circulating concentrations of fetal IL-6 and IL-8 in clinical chorioamnionitis ± birth asphyxia in term pregnancies are of fetal origin. Circulating fetal inflammatory cytokines are cleared by concentration-dependent placental mechanisms that are nearly saturated in chorioamnionitis ± fetal hypoxia. These observations provide additional insight into understanding the fetal immune response in term pregnancies complicated by clinical chorioamnionitis.
在足月妊娠并发绒毛膜羊膜炎的情况下，胎儿循环中细胞因子的来源和清除仍不清楚，胎盘的转运、合成和清除也不清楚。本研究的目的是确定（1）足月妊娠并发绒毛膜羊膜炎时胎儿和/或胎盘对炎症和抗炎细胞因子的合成和/或清除的贡献，以及（2）在进一步并发胎儿缺氧的情况下是否存在差异。
对妊娠 37 周以上的孕妇进行前瞻性队列研究，包括：第 1 组，无临产的单纯剖宫产（n=20）；第 2 组，单纯阴道分娩（n=30）；第 3 组，绒毛膜羊膜炎并发（n=10）；第 4 组，并发绒毛膜羊膜炎+胎儿缺氧（n=10）。检测脐动脉（UmA）和脐静脉（UmV）血中白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、肿瘤坏死因子-α（TNFα）和白细胞介素-10（IL-10）。
第 1 组 UmA 和 UmV 血中 IL-6 和 IL-8 低于检测下限，第 2 组增加（P<0.01），UmA>UmV（P<0.01）。第 3 组和第 4 组进一步增加（P=0.003），UmA>UmV。胎盘清除与浓度有关，在存在绒毛膜羊膜炎时接近饱和。
在绒毛膜羊膜炎中，胎儿 IL-6 和 IL-8 的合成明显增加。当并发胎儿缺氧时，合成增加。细胞因子的清除是通过胎盘浓度依赖性机制进行的，这可能导致胎儿不良影响。
在足月妊娠并发临床绒毛膜羊膜炎的情况下，胎盘在合成和/或清除炎症介质中的来源和作用尚不清楚；然而，传统观点认为胎盘是其来源。这是第一项研究表明，在足月妊娠并发临床绒毛膜羊膜炎和出生窒息的情况下，胎儿循环中 IL-6 和 IL-8 的浓度是胎儿来源的。通过胎盘浓度依赖性机制清除循环胎儿炎症细胞因子，在绒毛膜羊膜炎和胎儿缺氧时接近饱和。这些观察结果为理解足月妊娠并发临床绒毛膜羊膜炎时胎儿的免疫反应提供了更多的见解。
