Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung

Antenatal inflammation may be an important triggering event in the pathogenesis of bronchopulmonary dysplasia but may also accelerate fetal lung maturation. We examined the effects of intra-amniotic (IA) interleukin (IL)-1α and IL-1β on maturation of the fetal sheep lung. These cytokine effects were compared with IA endotoxin, a potent proinflammatory stimulus that accelerated lung maturation. Date-bred ewes received 15 or 150 μg recombinant ovine IL-1α or IL-1β or 10 mg Escherichia coli endotoxin by IA injection at 118 days gestation (term = 150 days), and fetuses were delivered at 125 days. IL-1α and IL-1β improved lung function and increased alveolar saturated phosphatidylcholine (Sat PC) and surfactant protein mRNA expression at the higher dose. The maturation response to IL-1α was greater than that to IL-1β, which was similar to endotoxin response. Inflammation was also more pronounced after IL-1α treatment. Only endotoxin animals had residual inflammation of the fetal membranes at 7 days. Lung compliance, lung volume, and alveolar Sat PC were positively correlated with residual alveolar wash leukocyte numbers 7 days after IL-1 treatment, suggesting a link between lung inflammation and maturation.