Iloprost Attenuates Hyperoxia-mediated Impairment of Lung Development in Newborn Mice

Cyclooxygenase-2 (COX-2/PTGS2) mediates hyperoxia-induced impairment of lung development in newborn animals, and is increased in lungs of human infants with bronchopulmonary dysplasia (BPD). COX-2 catalyzes production of cytoprotective prostaglandins such as prostacyclin (PGI2) as well as pro-inflammatory mediators such as thromboxane A2 (TxA2). Our objective was to determine whether iloprost, a synthetic analog of prostacyclin, would attenuate hyperoxia effects in the newborn mouse lung. To test this hypothesis, newborn C57BL/6 mice along with their dams were exposed to normoxia (21%) or hyperoxia (85% O2) from 4 to 14 days of age in combination with daily i.p. injections of either iloprost 200 µg/kg/day, nimesulide (selective COX-2 antagonist) 100 mg/kg/day, or vehicle. Alveolar development was estimated by Radial Alveolar Counts (RAC) and Mean Linear Intercepts (MLI). Lung function was determined on a flexiVent, and multiple cytokines and myeloperoxidase (MPO) were quantitated in lung homogenates. Lung...