title: Interleukin-1 in lipopolysaccharide induced chorioamnionitis in the fetal sheep.
abstract: We tested the hypothesis that interleukin 1 (IL-1) mediates intra-amniotic lipopolysaccharide (LPS)-induced chorioamnionitis in preterm fetal sheep. Time-mated Merino ewes with singleton fetuses received IL-1α, LPS, or saline (control) by intra-amniotic injection 1 to 2 days before operative delivery at 124 ± 1 days gestational age (N = 5-9/group; term = 150 days). Recombinant human IL-1 receptor antagonist (rhIL-1ra) was given into the amniotic fluid 3 hours before intra-amniotic LPS or saline to block IL-1 signaling. Inflammation in the chorioamnion was determined by histology, cytokine messenger RNA (mRNA), protein expression, and by quantitation of activated inflammatory cells. Intra-amniotic IL-1 and LPS both induced chorioamnionitis. However, IL-1 blockade with IL-1ra did not decrease intra-amniotic LPS-induced increases in pro-inflammatory cytokine mRNAs, numbers of inflammatory cells, myeloperoxidase, or monocyte chemotactic protein-1-expressing cells in the chorioamnion. We conclude that IL-1 and LPS both can cause chorioamnionitis, but IL-1 is not an important mediator of LPS-induced chorioamnionitis in fetal sheep.
authors.affiliation: Division of Pulmonary Biology/Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Berry
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: Noah H
authors.initials: NH
authors.lastname: Hillman
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kemp
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
mesh_terms: D000650:Amnion / Q000187:drug effects; D000818:Animals; D002821:Chorioamnionitis / Q000139:chemically induced / Q000503:physiopathology / Q000662:veterinary*; D016207:Cytokines / Q000032:analysis; D005260:Female; D005865:Gestational Age; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage; D007375:Interleukin-1 / Q000008:administration & dosage / Q000502:physiology*; D053582:Interleukin-1alpha / Q000008:administration & dosage; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D011247:Pregnancy; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep / Q000196:embryology*
chemical_list: D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053582:Interleukin-1alpha; D008070:Lipopolysaccharides; D011994:Recombinant Proteins