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

Suhas Kallapur, Boris Kramer, Ilias Nitsos, Jane Pillow, Jennifer Collins, Graeme Polglase, John Newnham, Alan Jobe

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29 Citations (Scopus)

Abstract

Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1alpha would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1alpha (100 mug) 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-1alpha injections (100 mug dose each): 7 days and again 1 day prior to delivery. IL-1alpha induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H(2)O(2) secretion was increased in inflammatory cells isolated from lungs of IL-1alpha-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1beta, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1alpha exposure. Lung volumes increased 7 days after intra-amniotic IL-1alpha 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-1alpha exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1alpha exposure. Compared with a single exposure, exposure to intra-amniotic IL-1alpha 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1alpha is a potent mediator of the fetal inflammatory response syndrome.
Original languageEnglish
Pages (from-to)L285 - L295
Number of pages11
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number3
DOIs
Publication statusPublished - 2011

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