Intra-amniotic endotoxin: chorioamnionitis precedes lung maturation in preterm lambs

The inflammatory and lung maturational effects of intra-amniotic exposure t o endotoxin were assessed in fetal lambs. Five hours to 25 days after intra amniotic injection of endotoxin, preterm lambs were delivered at 119-125 da ys gestation. Intra-amniotic endotoxin caused an inflammatory cell infiltra tion in amnion/chorion at 5 h, which persisted for 25 days. At 5-15 h after endotoxin, amnion/chorion cytokine mRNAs increased [12- to 26-fold for int erleukin (IL)-1 beta, IL-6, and IL-8 mRNA and 3-fold for tumor necrosis fac tor-alpha mRNA]. At 1-2 days after endotoxin, lung cytokine mRNAs increased 6- to 49-fold. Endotoxin caused modest changes in peripheral white blood c ell counts and no significant cytokine mRNA responses in fetal liver, place nta, or jejunum. Lung maturation, as characterized by increased lung volume s and alveolar saturated phosphatidylcholine, occurred at 7 days and persis ted for 25 days after endotoxin. We conclude that exposure to a single dose of intra-amniotic endotoxin causes inflammation and increases in cytokine mRNA in amnion/chorion and the fetal lung before lung maturation, consisten t with the hypothesis that proinflammatory cytokines signal lung maturation .