Antenatal endotoxin and glucocorticoid effects on lung morphometry in preterm lambs

In utero inflammation may accelerate fetal lung maturation but may also pla y a role in the pathogenesis of chronic lung disease. We examined the impac t of endotoxin, a potent proinflammatory stimulus, on structural and functi onal maturation of preterm sheep lungs. Date bred ewes received 20 mg Esche richia coli endotoxin or saline by ultrasound guided intra-amniotic injecti on at 119 d gestation. A comparison group of animals received 0.5 mg/kg bet amethasone, a known maturational agent, at 118 d gestation. Lambs were deli vered by cesarean section at 125 d (term = 150 d) and ventilated for 40 min . Lung function data are reported elsewhere. Total and differential white c ell counts were performed on amniotic fluid and fetal lung fluid samples. M orphometric analyses were performed on inflation fixed right upper lobes. T otal cell count increased slightly but not significantly in both amniotic f luid and fetal lung fluid. Both endotoxin and betamethasone had similar eff ects on alveolarization: average alveolar volume increased by approximately 20% and total alveolar number decreased by almost 30%. Both treatments led to thinning of alveolar walls, although this was statistically significant in the betamethasone-treated group only. Although antenatal endotoxin lead s to striking improvements in postnatal lung function, this may be at the e xpense of normal alveolar development.