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Effects of antenatal inflammation on the developing lung

Abstract:

The developing lung and immune systems are very plastic and their developmental pathway can be influenced by various endogenous and/or exogenous factors. In the last years translational research with various animal models has been helpful to answer some basic questions about the effect of chorioamnionitis on maturation and development of the foetal lung and immune system. Chorioamnionitis can induce a cascade of lung injury, pulmonary inflammation and remodelling in the foetal lung. Chorioamnionitis-induced IL-1 production is consistently associated with lung maturation, induced by enhancing surfactant protein and lipid synthesis. IL-1 therefore seems to be the main link between lung inflammation and lung maturation, which largely prevents RDS in preterm infants. On the other hand, chorioamnionitis can also cause structural lung changes and affect the expression of growth factors, like TGF-β, CTGF, FGF-10 or BMP-4, which are crucial for branching morphogenesis. These changes result in alveolar and microvascular simplification similar to BPD. Neonatal outcome may also be affected by chorioamnionitis by modulating the efficacy of the immune system. Chorioamnionitis can induce LPS-tolerance (endotoxin hyporesponsiveness/immunoparalysis), which may prevent further foetal lung damage but increases susceptibility to postnatal infections. The inflammatory and developmental signalling pathways affected by chorioamnionitis form delicately regulated networks, which interact with each other to control lung development. In addition to chorioamnionitis, these pathways can be affected by other prenatal (steroid) or postnatal factors (mechanical ventilation, oxygen exposure, infection, steroids). Because the postnatal response to injury appears to be highly dependent on prenatal exposures, the "secondary hito" hypothesis is very plausible, in which exposure to chorioamnionitis is a pbkp_redisposition for the development of adverse neonatal outcomes. © 2012 Georg Thieme Verlag KG Stuttgart New York.