Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs

Ilene R.S. Sosenko, Alan H. Jobe

Research output: Contribution to journalArticle

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Abstract

Proinflammatory stimulation resulting from intraamniotic endotoxin improves lung function, increases surfactant protein mRNA expression and protein content, increases alveolar and lung saturated phosphatidylcholine pools, and accelerates lung morphometric maturation in fetal sheep. The mechanism for induction of lung maturation does not involve an increase in fetal cortisol. The effect of endotoxin on the maturation of a different lung system, the antioxidant enzyme (AOE) system, has not been examined. Therefore, we hypothesized that intraamniotic endotoxin would produce acceleration of AOE activity in fetal sheep at similar doses and schedule of administration to those producing lung functional and surfactant maturation. In a dose-response study, intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:β5 endotoxin were administered 7 d before preterm delivery of sheep at 125 d gestation. In a study examining time interval of administration before delivery, 20 mg of endotoxin was injected at either 1-, 2-, 4-, 7-, or 15-d intervals before preterm delivery at 125 d. Doses of 1-100 mg of endotoxin produced significant increases in glutathione peroxidase activity; doses of 4-100 mg significantly increased catalase activity, whereas doses of 20-100 mg resulted in significant increases in total superoxide dismutase activity. Glutathione peroxidase activity was elevated within 2 d, whereas superoxide dismutase was increased by 4 d and catalase activity increased by 7 d after endotoxin. No AOE increases were sustained for 15 d. Endotoxin increased fetal lung AOE activity at similar dosing amounts and intervals to those producing maturation of lung function and surfactant. Thus, mechanisms involving proinflammatory stimulation, unrelated to glucocorticoid hormones, can induce maturation of the AOE system of the fetal lung.

Original languageEnglish (US)
Pages (from-to)679-683
Number of pages5
JournalPediatric Research
Volume53
Issue number4
DOIs
StatePublished - Apr 1 2003

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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