Antenatal inflammation can impair pulmonary maturation and potentially promote development of postnatal chronic lung disease. The purpose of our investigation is to evaluate how in utero exposure to maternal inflammation influences neonatal pulmonary function in a murine model. Our hypothesis was that inflammation leads to structural and functional airway changes that contribute to chronic diseases such as asthma.
Breeding colonies of C57/BL6 wild-type mice were established. On embryonic day 16 pregnant dams underwent intraperitoneal injections with sterile saline or with different concentrations of LPS (E. coli 055:B5) to induce maternal inflammation: 50 ug/kg, 200 ug/kg, 400 ug/kg. Dams spontaneously delivered and pups were monitored until postnatal day 21 when pulmonary function testing was performed using a SciReq FlexiVent system. Airway resistance, compliance and inspiratory capacity were assessed at baseline and in response to increasing concentrations of the bronchoconstrictor methacholine.
Intra-peritoneal LPS did not adversely influence maternal or neonatal mortality, or maternal failure to thrive during pregnancy. Neonatal pups were of comparable weight across groups. At postnatal day 21, LPS pups showed lower weight compared to controls, but there were no significant differences between the three different LPS dose groups. Airway resistance was increased with LPS, and importantly, LPS pups showed decreased airway compliance and inspiratory lung capacity compared to saline controls.
In this model of LPS-induced maternal inflammation, pulmonary function of the progeny is detrimentally impacted in terms of increased airway resistance, decreased airway compliance, and decreased inspiratory capacity. These changes represent characteristics of inflammatory reactive airway disease such as asthma. Future studies are needed to determine how antenatal inflammation alters neonatal pulmonary structure and airway function with the aim of developing novel therapeutic avenues.
© 2014 Published by Elsevier Inc.