Double exposure to intra-amniotic lipopolysaccharide and maternal betamethasone induces sustained increase of neutrophils in the lungs and disrupts alveolarization in newborn rats

Abstract

Aim: We investigated the combined effects of intra-amniotic lipopolysaccharide (LPS) and maternal betamethasone (BMZ) on alveolarization using a newborn rat model. Methods: LPS (1.0 mu g/sac) or vehicle was injected into the amniotic sacs of pregnant rats and BMZ (170 mu g/kg) or vehicle was injected intramuscularly into the pregnant rats twice at 8-h intervals on gestation day 20. The rat pups were delivered spontaneously after 2-2.5 days and raised until the measurements were taken. Bronchoalveolar lavage was performed on days 2 and 5, and morphometric analyses of the lungs were performed on days 5 and 14. Results: Intra-amniotic LPS significantly increased the neutrophils in the bronchoalveolar lavage fluid (BALF) on day 2, but double exposure to LPS and BMZ significantly alleviated the neutrophil increase in the BALF. On day 5, while the neutrophils in the BALF decreased in the animals exposed to LPS alone, the neutrophil numbers in the BALF were steady in the animals exposed to both LPS and BMZ. Morphometric analyses on days 5 and 14 revealed a significant disruption of alveolarization only in the animals exposed to both LPS and BMZ. Conclusions: Our results suggested that double exposure to maternal BMZ and intra-amniotic LPS induces sustained increase of neutrophils in the lungs and disrupts alveolarization.