title: Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep.
abstract: Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1α would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1α (100 μg) 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-1α injections (100 μg dose each): 7 days and again 1 day prior to delivery. IL-1α 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-1α-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1β, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1α exposure. Lung volumes increased 7 days after intra-amniotic IL-1α 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-1α exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1α exposure. Compared with a single exposure, exposure to intra-amniotic IL-1α 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1α is a potent mediator of the fetal inflammatory response syndrome.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Univ. of Cincinnati, Division of Pulmonary Biology, 3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. suhas.kallapur@cchmc.org
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Jennifer J P
authors.initials: JJ
authors.lastname: Collins
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
mesh_terms: D000650:Amnion; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D005315:Fetal Diseases / Q000276:immunology*; D005333:Fetus / Q000187:drug effects / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D053582:Interleukin-1alpha / Q000494:pharmacology*; D008168:Lung; D008198:Lymph Nodes / Q000378:metabolism; D008480:Mediastinitis / Q000473:pathology; D011247:Pregnancy; D034561:Sheep, Domestic
chemical_list: D051858:Forkhead Transcription Factors; D053582:Interleukin-1alpha