Document Detail

The interactive effects of endotoxin with prenatal glucocorticoids on short-term lung function in sheep.
MedLine Citation:
PMID:  11483927     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Previously we have shown that neonatal lung function in sheep after preterm birth is profoundly enhanced by intra-amniotic injection of endotoxin, with a magnitude at least equal to that induced by maternal betamethasone administration. This study investigated the effects of betamethasone on lung maturation and growth in the presence of inflammation by treating sheep with both maternal intramuscular betamethasone and intra-amniotic endotoxin injections. STUDY DESIGN: Time-mated pregnant ewes at 118 days' gestation were allocated at random to receive maternal intramuscular or intra-amniotic saline solution injection (n = 10), maternal intramuscular betamethasone injection (0.5 mg/kg; n = 7), intra-amniotic endotoxin injection (20 mg Escherichia coli B055;B5; n = 11) by ultrasonographic guidance, or both betamethasone and endotoxin injections (n = 7). The lambs were delivered abdominally at 125 days' gestation (term is 150 days' gestation), and the neonates were ventilated for 40 minutes before postmortem examination. RESULTS: Combined treatment with betamethasone and endotoxin resulted in significantly greater improvements in neonatal lung function than occurred after treatment with either agent alone, and this effect was not accompanied by a further increase in surfactant levels. The reduction in birth weight that is seen after maternal betamethasone treatment was not seen when this treatment was combined with endotoxin. Endotoxin treatment resulted in inflammatory responses in cord blood and alveolar wash, and these responses were not inhibited by betamethasone treatment. There were no pregnancy losses. CONCLUSION: Both intra-amniotic endotoxin injection and maternal intramuscular betamethasone injection promoted fetal lung maturation. When these treatments were combined, there were additive effects on short-term postnatal lung function but not on surfactant levels. Endotoxin negated the growth restriction in sheep caused by maternal betamethasone treatment. These findings provide evidence that the lung maturation induced by glucocorticoids and that induced by endotoxin are mediated by different mechanisms.
J P Newnham; T J Moss; J F Padbury; K E Willet; M Ikegami; M G Ervin; P Sly; A Jobe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  185     ISSN:  0002-9378     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-08-02     Completed Date:  2001-08-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  190-7     Citation Subset:  AIM; IM    
Women and Infants Research Foundation, Department of Obstetrics and Gynecology, University of Western Australia, Perth, Western Australia.
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MeSH Terms
Acute-Phase Reaction
Animals, Newborn / physiology
Betamethasone / administration & dosage,  pharmacology
Birth Weight
Carbon Dioxide / blood
Drug Interactions
Endotoxins / administration & dosage,  pharmacology*
Escherichia coli
Fetal Blood / chemistry
Gestational Age
Glucocorticoids / pharmacology*
Hydrogen-Ion Concentration
Leukocyte Count
Lung / drug effects,  embryology,  physiology*
Oxygen / blood
Grant Support
Reg. No./Substance:
0/Endotoxins; 0/Glucocorticoids; 124-38-9/Carbon Dioxide; 378-44-9/Betamethasone; 7782-44-7/Oxygen

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