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

Research output: Contribution to journalArticleResearchpeer-review

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

Cite this

Kallapur, Suhas G ; Nitsos, Ilias ; Moss, Timothy J M ; Polglase, Graeme R ; Pillow, Jane Jane ; Cheah, Fook-Choe ; 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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title = "IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide",
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.",
author = "Kallapur, {Suhas G} and Ilias Nitsos and Moss, {Timothy J M} and Polglase, {Graeme R} and Pillow, {Jane Jane} and Fook-Choe Cheah and Kramer, {Boris W} and Newnham, {John P} and Machiko Ikegami and Jobe, {Alan H}",
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language = "English",
volume = "179",
pages = "955 -- 961",
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issn = "1073-449X",
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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, Jane Jane; Cheah, Fook-Choe; Kramer, Boris W; Newnham, John P; Ikegami, Machiko; Jobe, Alan H.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 179, No. 10, 2009, p. 955 - 961.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - IL-1 mediates pulmonary and systemic inflammatory responses to chorioamnionitis induced by lipopolysaccharide

AU - Kallapur, Suhas G

AU - Nitsos, Ilias

AU - Moss, Timothy J M

AU - Polglase, Graeme R

AU - Pillow, Jane Jane

AU - Cheah, Fook-Choe

AU - Kramer, Boris W

AU - Newnham, John P

AU - Ikegami, Machiko

AU - Jobe, Alan H

PY - 2009

Y1 - 2009

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 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.

AB - 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.

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DO - 10.1164/rccm.200811-1728OC

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EP - 961

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

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