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.
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Publication status||Published - 2009|
Kallapur, S. G., Nitsos, I., Moss, T. J., Polglase, G., Pillow, J., Cheah, F-C., Kramer, B. W., Newnham, J., Ikegami, M., & Jobe, A. (2009). IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. American Journal of Respiratory Cell and Molecular Biology, 179(10), 955-961. https://doi.org/10.1164/rccm.200811-1728OC