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Am J Physiol Lung Cell Mol Physiol 280: L527-L536, 2001;
1040-0605/01 $5.00
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Vol. 280, Issue 3, L527-L536, March 2001

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

Suhas G. Kallapur1, Karen E. Willet2, Alan H. Jobe1, Machiko Ikegami1, and Cindy J. Bachurski1

1 Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039; and 2 TVW Telethon Institute For Child Health Research, Division of Clinical Sciences, University of Western Australia, Perth, Western Australia 6008, Australia

The inflammatory and lung maturational effects of intra-amniotic exposure to endotoxin were assessed in fetal lambs. Five hours to 25 days after intra-amniotic injection of endotoxin, preterm lambs were delivered at 119-125 days gestation. Intra-amniotic endotoxin caused an inflammatory cell infiltration 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 interleukin (IL)-1beta , IL-6, and IL-8 mRNA and 3-fold for tumor necrosis factor-alpha mRNA]. At 1-2 days after endotoxin, lung cytokine mRNAs increased 6- to 49-fold. Endotoxin caused modest changes in peripheral white blood cell counts and no significant cytokine mRNA responses in fetal liver, placenta, or jejunum. Lung maturation, as characterized by increased lung volumes and alveolar saturated phosphatidylcholine, occurred at 7 days and persisted 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, consistent with the hypothesis that proinflammatory cytokines signal lung maturation.

surfactant; cytokine; respiratory distress syndrome; bronchopulmonary dysplasia


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