Investigating pulmonary inflammation and injury after progressive systemic inflammation in preterm fetal sheep.

Introduction: 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. Methods: 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. Results: Repeated increasing doses of intravenous LPS decreased arterial pH, PaO Conclusion: 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.