Double exposure to intra-amniotic lipopolysaccharide and maternal betamethasone induces sustained increase of neutrophils in the lungs and disrupts alveolarization in newborn rats.
OBJECTIVE
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 μg/sac) or vehicle was injected into the amniotic sacs of pregnant rats and BMZ (170 μg/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.
Hyun Ju
HJ
Lee
Youn Jin
YJ
Lee
Heui Seung
HS
Jo
Chang Won
CW
Choi
Ee-Kyung
EK
Kim
Han-Suk
HS
Kim
Beyong Il
BI
Kim
Jung-Hwan
JH
Choi
D000650:Amnion; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D001623:Betamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000473:pathology*; D009504:Neutrophils / Q000187:drug effects*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000254:growth & development* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D001623:Betamethasone