Thrown off balance: the effect of antenatal inflammation on the developing lung and immune system

Steffen Kunzmann*, Jennifer J. P. Collins, Elke Kuypers, Boris W. Kramer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


In recent years, translational research with various animal models has been helpful to answer basic questions about the effect of antenatal inflammation on maturation and development of the fetal lung and immune system. The fetal lung and immune systems are very plastic and their development can be conditioned and influenced by both endogenous and/or exogenous factors. Antenatal inflammation can induce pulmonary inflammation, leading to lung injury and remodeling in the fetal lung. Exposure to antenatal inflammation can induce interleukin-1 alpha production, which enhances surfactant protein and lipid synthesis thereby promoting lung maturation. Interleukin-1 alpha is therefore a candidate for the link between lung inflammation and lung maturation, preventing respiratory distress syndrome in preterm infants. Antenatal inflammation can, however, cause structural changes in the fetal lung and affect the expression of growth factors, such as transforming growth factor-beta, connective tissue growth factor, fibroblast growth factor-10, or bone morphogenetic protein-4, which are essential for branching morphogenesis. These alterations cause alveolar and microvascular simplification resembling the histology of bronchopulmonary dysplasia. Antenatal inflammation may also affect neonatal outcome by modulating the responsiveness of the immune system. Lipopolysaccharide-tolerance (endotoxin hyporesponsiveness/immunoparalysis), induced by exposure to inflammation in utero, may prevent fetal lung damage, but increases susceptibility to postnatal infections. Moreover, prenatal exposure to inflammation appears to be a predisposition for the development of adverse neonatal outcomes, like bronchopulmonary dysplasia, if the preterm infant is exposed to a second postnatal hit, such as mechanical ventilation oxygen exposure, infections, or steroids.
Original languageEnglish
Pages (from-to)429-437
JournalAmerican Journal of Obstetrics and Gynecology
Issue number6
Publication statusPublished - Jun 2013


  • BPD
  • chorioamnionitis
  • immune modulation
  • RDS
  • surfactant
  • TGF-beta


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