Vandenberg E G, Kelly S B, Zahra V A, Lu H, Thiel A, Hooper S B, Galinsky R, Polglase G R
The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia.
Department of Paediatrics, Monash University, Melbourne, VIC, Australia.
Front Physiol. 2025 May 15;16:1542613. doi: 10.3389/fphys.2025.1542613. eCollection 2025.
Preterm birth and intrauterine inflammation are commonly associated with lung inflammation and remodeling. We developed a fetal inflammatory response model using increasing doses of intravenous lipopolysaccharide (LPS) to cause systemic inflammation and injury. However, the effects of an increasing systemic inflammatory response on fetal lung inflammation and injury are not known. We aimed to investigate the effect of repeated increasing doses of intravenous LPS on pulmonary inflammation and injury in preterm fetal sheep.
Fetal sheep at 124 days of gestation (term ∼148 days) underwent surgical instrumentation. At 129 days of gestation, fetal sheep were randomized to saline control (n = 8) or repeated LPS infusions (300 ng/24 h then doubled every 24 h for 2 days; n = 8). Four days after LPS/saline infusions commenced, fetal lungs were collected for histological and molecular analysis of markers of pulmonary inflammation and injury.
Repeated increasing doses of intravenous LPS decreased arterial pH, PaO, SaO and increased lactate and PaCO compared to controls. LPS infusions caused a decrease in mRNA expression of pro-inflammatory cytokines (p = 0.030) and (p = 0.034) and an increase in (p < 0.0001). LPS exposure did not alter histological assessment of airway structure, elastin or collagen abundance, inflammatory cell infiltration or cell death compared to controls.
Intravenous administration of LPS did not cause fetal lung inflammation and injury assessed 4 days after LPS infusions commenced. Direct exposure to endotoxins within the lungs may be necessary to induce inflammation and injury in the fetal lungs.
早产和宫内炎症通常与肺部炎症及重塑有关。我们通过递增静脉注射脂多糖（LPS）剂量建立了一种胎儿炎症反应模型，以引发全身炎症和损伤。然而，全身炎症反应增强对胎儿肺部炎症和损伤的影响尚不清楚。我们旨在研究重复递增剂量静脉注射LPS对早产胎羊肺部炎症和损伤的影响。
妊娠124天（足月约148天）的胎羊接受手术器械植入。在妊娠129天，将胎羊随机分为生理盐水对照组（n = 8）或重复LPS输注组（300 ng/24 h，然后每24小时剂量翻倍，共2天；n = 8）。在开始LPS/生理盐水输注4天后，收集胎儿肺组织，进行肺部炎症和损伤标志物的组织学和分子分析。
与对照组相比，重复递增剂量静脉注射LPS使动脉pH、PaO、SaO降低，乳酸和PaCO升高。LPS输注导致促炎细胞因子的mRNA表达降低（p = 0.030）和（p = 0.034），而升高（p < 0.0001）。与对照组相比，LPS暴露未改变气道结构、弹性蛋白或胶原蛋白丰度、炎症细胞浸润或细胞死亡的组织学评估。
静脉注射LPS在开始输注LPS 4天后并未引起胎儿肺部炎症和损伤。可能需要直接暴露于肺内毒素才能诱导胎儿肺部炎症和损伤。
