Intra-amniotic injection of IL-1 induces inflammation and maturation in fetal sheep lung

Am J Physiol Lung Cell Mol Physiol. 2002 Mar;282(3):L411-20. doi: 10.1152/ajplung.00097.2001.

Abstract

Antenatal inflammation may be an important triggering event in the pathogenesis of bronchopulmonary dysplasia but may also accelerate fetal lung maturation. We examined the effects of intra-amniotic (IA) interleukin (IL)-1 alpha and IL-1 beta on maturation of the fetal sheep lung. These cytokine effects were compared with IA endotoxin, a potent proinflammatory stimulus that accelerated lung maturation. Date-bred ewes received 15 or 150 microg recombinant ovine IL-1 alpha or IL-1 beta or 10 mg Escherichia coli endotoxin by IA injection at 118 days gestation (term = 150 days), and fetuses were delivered at 125 days. IL-1 alpha and IL-1 beta improved lung function and increased alveolar saturated phosphatidylcholine (Sat PC) and surfactant protein mRNA expression at the higher dose. The maturation response to IL-1 alpha was greater than that to IL-1 beta, which was similar to endotoxin response. Inflammation was also more pronounced after IL-1 alpha treatment. Only endotoxin animals had residual inflammation of the fetal membranes at 7 days. Lung compliance, lung volume, and alveolar Sat PC were positively correlated with residual alveolar wash leukocyte numbers 7 days after IL-1 treatment, suggesting a link between lung inflammation and maturation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amnion
  • Amniotic Fluid / cytology
  • Animals
  • Animals, Newborn / physiology
  • Delivery, Obstetric
  • Embryonic and Fetal Development / drug effects
  • Fetal Organ Maturity
  • Fetus / drug effects
  • Fetus / physiology
  • Forecasting
  • Injections
  • Interleukin-1 / administration & dosage*
  • Interleukin-1 / pharmacology
  • Leukocyte Count
  • Lung / embryology*
  • Lung / physiology
  • Pneumonia / chemically induced*
  • Pulmonary Surfactants / genetics
  • Pulmonary Surfactants / metabolism
  • RNA, Messenger / metabolism
  • Respiration
  • Sheep

Substances

  • Interleukin-1
  • Pulmonary Surfactants
  • RNA, Messenger