title: IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide.
abstract: BACKGROUND
  Chorioamnionitis frequently associates with preterm delivery and increased amniotic fluid IL-1, and causes fetal lung and systemic inflammation. However, chorioamnionitis is also associated with a paradoxical reduction in the incidence of surfactant deficiency-related respiratory distress syndrome in preterm infants.
  
  
  OBJECTIVE
  To identify the role of IL-1 signaling in the mediation of pulmonary and systemic inflammation and lung maturation in a fetal sheep model of lipopolysaccharide (LPS) induced chorioamnionitis.
  
  
  METHODS
  After confirming the efficacy of recombinant human IL-1 receptor antagonist (rhIL-1ra), fetal sheep were exposed to intraamniotic (IA) injections of Escherichia coli LPS with or without prior IA injections of rhIL-1ra. Preterm lambs were delivered at 82% of term gestation.
  
  
  RESULTS
  rhIL-1ra decreased IA LPS-induced lung inflammation assessed by decreased lung neutrophil and monocyte influx, inducible nitric oxide synthase expression, lung IL-6 and IL-1beta mRNA expression, and airway myeloperoxidase concentrations. rhIL-1ra inhibited IA LPS-induced fetal systemic inflammation assessed by decreased plasma IL-8, protein carbonyls, blood neutrophilia, and the expression of serum amyloid A3 mRNA in the liver. rhIL-1ra also partially blocked the lung maturational effects of IA LPS. Therefore blockade of IL-1 signaling in the amniotic compartment inhibited fetal lung and systemic inflammation and lung maturation in response to LPS-induced chorioamnionitis.
  
  
  CONCLUSIONS
  IL-1 plays a central role in the pathogenesis of chorioamnionitis-induced fetal inflammatory responses.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA. suhas.kallapur@cchmc.org
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Ilias
authors.initials: I
authors.lastname: Nitsos
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.forename: J Jane
authors.initials: JJ
authors.lastname: Pillow
authors.forename: Fook-Choe
authors.initials: FC
authors.lastname: Cheah
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002821:Chorioamnionitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000276:immunology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012756:Sheep; D015398:Signal Transduction
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins