IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide

Am J Respir Crit Care Med. 2009 May 15;179(10):955-61. doi: 10.1164/rccm.200811-1728OC. Epub 2009 Feb 20.


Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chorioamnionitis / immunology*
  • Chorioamnionitis / metabolism
  • Chorioamnionitis / pathology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fetus / drug effects
  • Fetus / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1alpha / antagonists & inhibitors
  • Interleukin-1alpha / immunology*
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / antagonists & inhibitors
  • Lung / drug effects
  • Lung / embryology*
  • Lung / immunology
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pregnancy
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / immunology
  • Receptors, Interleukin-1 / metabolism
  • Recombinant Proteins / pharmacology
  • Sheep
  • Signal Transduction


  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1alpha
  • Interleukin-1beta
  • Lipopolysaccharides
  • Receptors, Interleukin-1
  • Recombinant Proteins