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, J. Jane Pillow, Cheah Fook Choe, Boris W. Kramer, John P. Newnham, Machiko Ikegami, Alan H. Jobe

Research output: Contribution to journalArticle

88 Citations (Scopus)

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 intra-amniotic (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.

Original languageEnglish
Pages (from-to)955-961
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume179
Issue number10
DOIs
Publication statusPublished - 15 May 2009
Externally publishedYes

Fingerprint

Chorioamnionitis
Interleukin-1
Interleukin-1 Receptors
Lipopolysaccharides
Lung
Pneumonia
Sheep
Messenger RNA
Injections
Nitric Oxide Synthase Type II
Amniotic Fluid
Interleukin-8
Amyloid
Premature Infants
Surface-Active Agents
Peroxidase
Blood Proteins
Monocytes
Interleukin-6
Neutrophils

Keywords

  • Bronchopulmonary dysplasia
  • Innate immunity
  • Interleukin-1 receptor
  • Preterm birth
  • Respiratory distress syndrome

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. / Kallapur, Suhas G.; Nitsos, Ilias; Moss, Timothy J M; Polglase, Graeme R.; Pillow, J. Jane; Fook Choe, Cheah; Kramer, Boris W.; Newnham, John P.; Ikegami, Machiko; Jobe, Alan H.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 10, 15.05.2009, p. 955-961.

Research output: Contribution to journalArticle

Kallapur, SG, Nitsos, I, Moss, TJM, Polglase, GR, Pillow, JJ, Fook Choe, C, Kramer, BW, Newnham, JP, Ikegami, M & Jobe, AH 2009, 'IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide', American Journal of Respiratory and Critical Care Medicine, vol. 179, no. 10, pp. 955-961. https://doi.org/10.1164/rccm.200811-1728OC
Kallapur, Suhas G. ; Nitsos, Ilias ; Moss, Timothy J M ; Polglase, Graeme R. ; Pillow, J. Jane ; Fook Choe, Cheah ; Kramer, Boris W. ; Newnham, John P. ; Ikegami, Machiko ; Jobe, Alan H. / IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide. In: American Journal of Respiratory and Critical Care Medicine. 2009 ; Vol. 179, No. 10. pp. 955-961.
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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 intra-amniotic (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.",
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AU - Nitsos, Ilias

AU - Moss, Timothy J M

AU - Polglase, Graeme R.

AU - Pillow, J. Jane

AU - Fook Choe, Cheah

AU - Kramer, Boris W.

AU - Newnham, John P.

AU - Ikegami, Machiko

AU - Jobe, Alan H.

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N2 - 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 intra-amniotic (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.

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KW - Bronchopulmonary dysplasia

KW - Innate immunity

KW - Interleukin-1 receptor

KW - Preterm birth

KW - Respiratory distress syndrome

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