Betamethasone effects on chorioamnionitis induced by intra-amniotic endotoxin in sheep

John Newnham, Suhas Kallapur, Boris Kramer, Timothy Moss, Ilias Nitsos, Machiko Ikegami, Alan Jobe

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Abstract

OBJECTIVE: Intra-amniotic administration of endotoxin in sheep is a model of subclinical chorioamnionitis. Intrauterine inflammation alters lung development to improve postnatal lung function and may predispose the infant to lung and brain injury. We describe the effects of intra-amniotic endotoxin on cytokines and white cell responses in the membranes and amniotic fluid and investigate the hypothesis that betamethasone treatment suppresses these responses. STUDY DESIGN: Pregnant ewes were allocated at random to receive either intra-amniotic saline solution (control animals), maternal intramuscular betamethasone, intra-amniotic endotoxin by ultrasound guidance (10 mg Escherichia coli 055:B5), or a combination of the betamethasone and endotoxin treatments. Lambs were delivered abdominally at 110 to 125 days of gestation at time points that ranged from 2 hours to 15 days after treatment. RESULTS: When compared with saline solution-injected control animals, the intra-amniotic injection of endotoxin increased white cell counts in amniotic fluid. Levels of interleukin-8, but not interleukin-6, were significantly increased in amniotic fluid from 5 hours to 15 days after intra-amniotic endotoxin injection, and interleukin-8 levels were not decreased by concurrent treatment with betamethasone. After endotoxin treatment, interleukin-1beta and interleukin-8 messenger RNA were expressed in chorion, and interleukin-6 messenger RNA expression was localized to chorionic blood vessel epithelium. The half-life of endotoxin in the amniotic fluid was 1.7 days, and levels remained measurable 15 days after injection.
Original languageEnglish
Pages (from-to)1458 - 1466
Number of pages9
JournalAmerican Journal of Obstetrics and Gynecology
Volume189
Issue number5
Publication statusPublished - 2003
Externally publishedYes

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