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.

• Authors: Suhas G Kallapur, Ilias Nitsos, Timothy J M Moss, Graeme R Polglase, J Jane Pillow, Fook-Choe Cheah, Boris W Kramer, John P Newnham, Machiko Ikegami, Alan H Jobe
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 179 Issue 10 Pg. 955-61 (May 15 2009) ISSN: 1535-4970 [Electronic] United States
• PMID: 19234101 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1alpha
• Interleukin-1beta
• Lipopolysaccharides
• Receptors, Interleukin-1
• Recombinant Proteins

Topics

• Animals
• Bronchoalveolar Lavage Fluid (chemistry)
• Chorioamnionitis (immunology, metabolism, pathology)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Female
• Fetus (drug effects, immunology)
• Humans
• Interleukin 1 Receptor Antagonist Protein (pharmacology)
• Interleukin-1alpha (antagonists & inhibitors, immunology, metabolism)
• Interleukin-1beta (antagonists & inhibitors, immunology, metabolism)
• Lipopolysaccharides (administration & dosage, antagonists & inhibitors)
• Lung (drug effects, embryology, immunology)
• Pneumonia (immunology, metabolism, pathology)
• Pregnancy
• Receptors, Interleukin-1 (antagonists & inhibitors, immunology, metabolism)
• Recombinant Proteins (pharmacology)
• Sheep
• Signal Transduction