Antenatal betamethasone attenuates intrauterine infection-aggravated hyperoxia-induced lung injury in neonatal rats

Abstract

Background: Intrauterine infection can exacerbate postnatal hyperoxic lung injury. We hypothesized that antenatal betamethasone treatment attenuates hyperoxic lung injury aggravated by intrauterine infection in neonatal rats. Methods: Newborn Sprague-Dawley rats were divided into eight experimental groups according to (i) whether rats were exposed to normoxia (N) or hyperoxia (H, 85% oxygen) from postnatal day (P)1 to P14, (ii) whether antenatal betamethasone (0.2 mg/dose) or vehicle was administered to pregnant rats at gestation days (E)19 and E20, and (iii) whether intrauterine infection was induced or not antenatally. Intrauterine infection was induced by intracervical inoculation of Escherichia coli into pregnant rats on E19. We measured cytokine levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in P1 rat lungs and performed morphometric analyses and assessed inflammatory responses in lung tissue and bronchoalveolar lavage (BAL) at P14 by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining and measurement of myeloperoxidase activity, collagen, and cytokine levels. results: Cytokine levels in P1 rat lungs were increased by intrauterine infection, and these increases were attenuated by antenatal betamethasone. Hyperoxic lung injuries, indicated by morphometric changes and an inflammatory response in the lung and BAL fluid, were aggravated by intrauterine infection at P14. This aggravation was significantly attenuated by antenatal betamethasone. conclusion: Antenatal betamethasone attenuated aggravated hyperoxic lung injuries induced by intrauterine infection in neonatal rats via its anti-inflammatory actions.

Postnatal inflammation in the pathogenesis of bronchopulmonary dysplasia

“…However, the authors noted that 2 weeks of hyperoxia caused extensive lung injury, perhaps, masking the effect of LPS (Choi et al, ). Similarly, enhancement of lung injury has been reported by other investigators, by postnatal hyperoxia exposure, with intra‐amniotic priming to LPS (Kim et al, ; Lee et al, ; Velten et al, ), with attenuation of these effects by antenatal betamethasone (Yoo et al, ).…”

Recent advances in the mechanisms of lung alveolarization and the pathogenesis of bronchopulmonary dysplasia

“…With antenatal inflammation in mind, several animal models of BPD have been developed to include an intrauterine inflammation component, which is translatable to the clinic, as described above for intrauterine Ureoplasma infection in sheep (73). Related intrauterine inflammation models have been reported in rats to study the utility of antenatal glucocorticoids to influence lung development in the background of antenatal inflammation (378). Studies have also examined NF-B function in the endothelium (329).…”

Animal Models, Learning Lessons to Prevent and Treat Neonatal Chronic Lung Disease

“…However, postnatal exposure to 65% oxygen has the opposite effect of accelerated lung growth and attenuated pulmonary hypertension. A second example is the competing effects of intracervical E. coli and betamethasone on postnatal hyperoxic exposures in rats ( 146 ). The hyperoxic responses were increased by the antenatal inflammation but attenuated by the combination of inflammation and betamethasone.…”