Intra-amniotic endotoxin induces lung maturation by direct effects on the developing respiratory tract in preterm sheep

Objective: Our purpose was to determine whether improved preterm lung function caused by intraamniotic endotoxin treatment requires endotoxin entry into the respiratory tract. Study Design: We assessed lung inflammation 2 days after intra-amniotic endotoxin (10 mg, Escherichia coli 055:B5) or saline solution in preterm lambs (123 daysʹ gestation) that had undergone surgery to isolate the gastrointestinal or respiratory systems from the amniotic sac. In other sheep longer-term effects were assessed 7 days after we isolated the fetal respiratory tract and gave endotoxin or saline solution directly to the lungs or into the amniotic sac. We measured pulmonary inflammation, lung function, and surfactant 1 week after treatment (~125 days). Results: Pulmonary inflammation was present after intra-amniotic endotoxin only if there was communication between the respiratory tract and the amniotic sac. Lung function was improved and surfactant was increased only in preterm lambs that received direct pulmonary endotoxin. Conclusion: Endotoxin causes functional improvement of the preterm lung by direct effects on the developing respiratory system. (Am J Obstet Gynecol 2002;187:1059-65.)