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.
|Pages (from-to)||955 - 961|
|Number of pages||7|
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Publication status||Published - 2009|
Kallapur, S. G., Nitsos, I., Moss, T. J. M., Polglase, G. R., Pillow, J. J., Cheah, F-C., Kramer, B. W., Newnham, J. P., Ikegami, M., & Jobe, A. H. (2009). IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. American Journal of Respiratory and Critical Care Medicine, 179(10), 955 - 961. https://doi.org/10.1164/rccm.200811-1728OC