This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200811-1728OCv1 179/10/955    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kallapur, S. G. Articles by Jobe, A. H. Search for Related Content PubMed PubMed Citation Articles by Kallapur, S. G. Articles by Jobe, A. H.

IL-1 Mediates Pulmonary and Systemic Inflammatory Responses to Chorioamnionitis Induced by Lipopolysaccharide

¹ Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio; ² School of Women's and Infants' Health, University of Western Australia, Perth, Australia; and ³ Department of Pediatrics, Maastricht University Medical Center, Maastricht, The Netherlands

Correspondence and requests for reprints should be addressed to Suhas G. Kallapur, M.D., Cincinnati Children's Hospital Medical Center, University of Cincinnati, Division of Pulmonary Biology, 3333 Burnet Avenue, Cincinnati, OH 45229-3039. E-mail: suhas.kallapur{at}cchmc.org

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-1β 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.

Key Words: respiratory distress syndrome • bronchopulmonary dysplasia • preterm birth • interleukin-1 receptor • innate immunity

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Chorioamnionitis is associated with pulmonary and systemic inflammation, an increase in pulmonary surfactant, and organ injury responses in the fetus. The mediator/s of these responses are not known. What This Study Adds to the Field Inhibition of IL-1 signaling in the amniotic compartment decreased pulmonary and systemic inflammation and reversed lung maturation responses in a fetal sheep model of chorioamnionitis induced by intraamniotic injection of lipopolysaccharide.

 

This article has been cited by other articles:

				S. G. Kallapur, T. J. M. Moss, R. L. Auten Jr., I. Nitsos, J. J. Pillow, B. W. Kramer, D. Y. Maeda, J. P. Newnham, M. Ikegami, and A. H. Jobe IL-8 signaling does not mediate intra-amniotic LPS-induced inflammation and maturation in preterm fetal lamb lung Am J Physiol Lung Cell Mol Physiol, September 1, 2009; 297(3): L512 - L519. [Abstract] [Full Text] [PDF]