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

Suhas G Kallapur, Ilias Nitsos, Timothy J M Moss, Graeme R Polglase, Jane Jane Pillow, Fook-Choe Cheah, Boris W Kramer, John P Newnham, Machiko Ikegami, Alan H Jobe

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Abstract

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.
Original languageEnglish
Pages (from-to)955 - 961
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume179
Issue number10
DOIs
Publication statusPublished - 2009
Externally publishedYes

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