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Am. J. Respir. Crit. Care Med., Volume 162, Number 5, November 2000, 1656-1661

Endotoxin-induced Lung Maturation in Preterm Lambs Is Not Mediated by Cortisol

ALAN H. JOBE, JOHN P. NEWNHAM, KAREN E. WILLET, TIMOTHY J. MOSS, M. GORE ERVIN, JAMES F. PADBURY, PETER SLY, and MACHIKO IKEGAMI

Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio; Women and Infants Research Foundation, Department of Obstetrics, and TVW Telethon Institute for Child Health Research, Division of Clinical Science, University of Western Australia, Perth, Australia; Department of Biology, Middle Tennessee State University, Murfreesboro, Tennessee; and Women and Infants Hospital, Providence, Rhode Island

Antenatal exposure to glucocorticoids, amnionitis, intraamniotic interleukin (IL)-1alpha , or endotoxin can improve postnatal lung function after preterm delivery. The relationship between early lung maturation and the dose and duration of a proinflammatory stimulus has not been evaluated. The effects of proinflammatory stimuli on fetal plasma cortisol also have not been evaluated. We hypothesized that intraamniotic endotoxin would induce early lung maturation in fetal sheep without increasing fetal cortisol. Intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:beta 5 endotoxin caused 2-fold increases in compliance, 4- to 5-fold increases in lung gas 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. Increases in Sat PC in lung tissue and alveolar washes were detected 2 d after endotoxin 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 resulted in lung maturation responses equivalent to single dose comparison groups without elevations in cortisol. Early lung maturation induced by intraamniotic endotoxin in fetal sheep occurred without an increase in fetal plasma cortisol, indicating that endotoxin promoted lung maturation by a mechanism independent of cortisol.




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