Endotoxin-induced lung maturation in preterm lambs is not mediated by cortisol

Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleuki n (IL)-1 alpha, or endotoxin can improve postnatal lung function after pret erm delivery. The relationship between early lung maturation and the dose a nd duration of a proinflammatory stimulus has not been evaluated. The effec ts of proinflammatory stimuli on fetal plasma cortisol also have not been e valuated. We hypothesized that intraamniotic endotoxin would induce early l ung maturation in fetal sheep without increasing fetal cortisol. Intraamnio tic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:beta5 endotox in caused 2-fold increases in compliance, 4- to 5-fold increases in lung ga s volumes, and 20-fold increases in alveolar saturated phosphatidylcholine (Sat PC) when given 7 d before preterm delivery at 125 d gestation. Animals treated with 20 mg endotoxin for treatment to delivery intervals of 5 h to 15 d had no significant elevations in cord plasma cortisol levels. Increas es in Sat PC in lung tissue and alveolar washes were detected 2 d after end otoxin treatment and lung function improved 4 d after endotoxin treatment. Two doses of endotoxin given 3 and 7 d or 7 and 15 d before treatment resul ted in Lung maturation responses equivalent to single dose comparison group s without elevations in cortisol. Early lung maturation induced by intraamn iotic endotoxin in fetal sheep occurred without an increase in fetal plasma cortisol, indicating that endotoxin promoted lung maturation by a mechanis m independent of cortisol.