期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 179, 期 10, 页码 955-961出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.200811-1728OC
关键词
respiratory distress syndrome; bronchopulmonary dysplasia; preterm birth; interleukin-1 receptor; innate immunity
资金
- NIH [HD-057869, AI-069716, HL-65397]
- Grow Research Institute, University of Maastricht, NWO [016.096.141]
- NHMRC, Australia [CDA-303261]
- NHFA
- Viertel SMRF, Australia
- WIRF
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 (LIPS) 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-1 beta 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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