Effects of antenatal endotoxin and glucocorticoids on the lungs of preterm lambs

Abstract

OBJECTIVE We hypothesized that the proinflammatory response to intra-amniotic endotoxin would induce lung maturation in preterm lambs. STUDY DESIGN Ewes were randomly assigned to receive 20 mg Escherichia coli endotoxin by intra-amniotic injection, maternal betamethasone (0.5 mg/kg), or sodium chloride solution. Preterm lambs were delivered at 125 days' gestation and underwent ventilation to assess lung function. Lung gas volume, surfactant concentrations, and inflammation were subsequently evaluated, with data analyzed by analysis of variance. RESULTS Fetal endotoxin exposure 6 days before delivery increased compliance by 59%, increased lung gas volume 2.3-fold, increased concentrations of surfactant lipids, increased surfactant A and B protein levels, and increased messenger ribonucleic acid expressions for surfactant proteins (all P <.01, vs control group). Betamethasone exposure resulted in less consistent effects. White blood cell counts were increased in fetal membranes and lungs after endotoxin exposure, but there was no severe inflammation. CONCLUSION A single fetal exposure to endotoxin resulted in large improvements in postnatal lung function and increases in surfactant concentrations after preterm delivery. These effects were qualitatively larger than those achieved with betamethasone.