IL-1α Causes Lung Inflammation and Maturation by Direct Effects on Preterm Fetal Lamb Lungs

Intra-amniotic endotoxin induces IL-1, causeschorioamnionitis, lung inflammation, lung injury and lung maturation in preterm lambs. Intra-ammotic IL-1 alpha also causes chorioamnionitis, lung inflammation and lung maturation. We asked if IL-1 alpha effects on the preterm lung are mediated by direct signaling to the lung rather than by indirect effects from the chorioamnionitis. To study IL-1 effects independently of chorioamnionitis, the lungs and the amniotic fluid were surgically separated in fetal sheep by diverting fetal lung fluid via a tracheostomy tube to a sialastie bag. A mini-osmotic pump delivered an intratracheal infusion of recombinant sheep IL-1 alpha (10 mu g) or saline (control) over 24 h. Pretenn lambs were delivered 1d or 7d after the start of the infusion at 124d gestational age (Term = 150d). IL-1 alpha recruited inflammatory cells and increased proinflammatory cytokine mRNA expression in the fetal lungs. Compared with controls, IL-1 alpha did not alter lung antioxidant enzyme activity or alveolar numbers. IL-1 alpha had minimal effects on the mRNA or protein expression of proteins essential for vascular development. IL-1 alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1 alpha.