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

S.G. Kallapur, Ilias Nitsos, T.J. Moss, Graeme Polglase, Jane Pillow, F-C. Cheah, B.W. Kramer, John Newnham, M. Ikegami, Alan Jobe

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    Rationale: Chorioamnionitis frequently associates with preterm deliveryand increased amniotic fluid IL-1, and causes fetal lungand systemic inflammation. However, chorioamnionitis is also associatedwith a paradoxical reduction in the incidence of surfactantdeficiency–related respiratory distress syndrome in preterm infants.Objectives: To identify the role of IL-1 signaling in the mediation ofpulmonary andsystemicinflammation and lung maturation in a fetalsheep model of lipopolysaccharide (LPS) induced chorioamnionitis.Methods: After confirming the efficacy of recombinant human IL-1receptor antagonist (rhIL-1ra), fetal sheep were exposed to intraamniotic(IA) injections of Escherichia coli LPS with or without prior IAinjections of rhIL-1ra. Preterm lambs were delivered at 82% of termgestation.Measurements and Main Results: rhIL-1ra decreased IA LPS–inducedlung inflammation assessed by decreased lung neutrophil andmonocyte influx, inducible nitric oxide synthase expression, lungIL-6 and IL-1b mRNA expression, and airway myeloperoxidaseconcentrations. rhIL-1ra inhibited IA LPS–induced fetal systemicinflammation assessed by decreased plasma IL-8, protein carbonyls,blood neutrophilia,andthe expression of serumamyloidA3mRNAinthe liver. rhIL-1ra also partially blocked the lung maturational effectsof IA LPS. Therefore blockade of IL-1 signaling in the amnioticcompartment inhibited fetal lung and systemic inflammation andlung maturation in response to LPS-induced chorioamnionitis.Conclusions: IL-1 plays a central role in the pathogenesis ofchorioamnionitis-induced fetal inflammatory responses.
    Original languageEnglish
    Pages (from-to)955-961
    JournalAmerican Journal of Respiratory Cell and Molecular Biology
    Issue number10
    Publication statusPublished - 2009


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