Cyclooxygenase-2 inhibition partially protects against 60% O2 -mediated lung injury in neonatal rats.

RationaleUse of the anti-inflammatory agent dexamethasone in premature infants with bronchopulmonary dysplasia has been curtailed, and no alternative anti-inflammatory agents are approved for this use. Our objective was to use a neonatal rat model of bronchopulmonary dysplasia to determine if an highly selective cyclooxygenase-2 inhibitor, 5,5-dimethyl-3-(3-fluorophenyl)4-(4-methylsulfonyl)phenyl-2(5H)-furanone (DFU; 10 mu g/g body weight), could prevent inflammatory cell influx and protect against lung injury. MethodsNeonatal rats exposed to air or 60% O-2 for 14 days from birth either received daily i.p. injections of (i) vehicle or DFU or (ii) vehicle or an EP(1) receptor antagonist, SC-19220. ResultsDFU attenuated the lung macrophage and neutrophil influx, prevented interstitial thickening and prevented the loss of peripheral blood vessels induced by 60% O-2, but did not protect against the variance in alveolar diameter induced by 60% O-2. Exposure to 60% O-2 caused both an increase in lung prostaglandin E-2 content and a reduction in lung mesenchymal cell mass which was reversed by DFU. Prostaglandin E-2 binding to the EP(1) receptor inhibited DNA synthesis in cultures of lung fibroblasts in a dose dependent fashion. Treatment with SC-19220 attenuated the reduction in lung mesenchymal mass observed following exposure of rat pups to 60% O-2. ConclusionsAn highly selective cyclooxygenase-2 inhibitor is an effective anti-inflammatory substitute for dexamethasone for preventing phagocyte influx into the neonatal lung during 60% O-2-mediated lung injury, and can modify the severity of that injury. Pediatr Pulmonol. 2014; 49:991-1002. (c) 2013 Wiley Periodicals, Inc.