Pulmonary and systemic inflammatory responses to intra-amniotic IL-1 alpha in fetal sheep

Suhas G. Kallapur*, Boris W. Kramer, Ilias Nitsos, J. Jane Pillow, Jennifer J. P. Collins, Graeme R. Polglase, John P. Newnham, Alan H. Jobe

*Corresponding author for this work

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Kallapur SG, Kramer BW, Nitsos I, Pillow JJ, Collins JJP, Polglase GR, Newnham JP, Jobe AH. Pulmonary and systemic inflammatory responses to intra-amniotic IL-1 alpha in fetal sheep. Am J Physiol Lung Cell Mol Physiol 301: L285-L295, 2011. First published June 10, 2011; doi:10.1152/ajplung.00446.2010.-Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1 alpha would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1 alpha (100 mu g) and were delivered 1, 3, or 7 days later, at 124 +/- 1 days gestation (n = 5-8/group). A separate group of sheep were given two intra-amniotic IL-1 alpha injections (100 mu g dose each): 7 days and again 1 day prior to delivery. IL-1 alpha induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H2O2 secretion was increased in inflammatory cells isolated from lungs of IL-1 alpha-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1 beta, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1 alpha exposure. Lung volumes increased 7 days after intra-amniotic IL-1 alpha exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1 alpha exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1 alpha exposure. Compared with a single exposure, exposure to intra-amniotic IL-1 alpha 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1 alpha is a potent mediator of the fetal inflammatory response syndrome.
Original languageEnglish
Pages (from-to)L285-L295
JournalAmerican Journal of Physiology-Lung Cellular and Molecular Physiology
Issue number3
Publication statusPublished - Sept 2011


  • prematurity
  • bronchopulmonary dysplasia
  • chorioamnionitis
  • fetal inflammatory response syndrome

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