Role of polymorphonuclear leukocytes in hyperoxic lung injury. Prevention of neutrophil influx into the lung endothelium during oxygen exposure by ibuprofen.

The present study examines the role of PMN in hyperoxic lung injury using a nonsteroidal anti-inflammatory drug, ibuprofen. New Zealand white rabbits were exposed to 100% oxygen or air for 1 to 4 days. The animals were divided into two groups: the treatment group received ibuprofen with drinking water, and the control group received water alone. After exposure to oxygen or air, the rabbits were injected with indium-III-oxine labeled PMN. Influx or radioactive PMN into the lung was detected using gamma scintigraphic technique only in 72 h and 96 h oxygen-exposed animals which were not treated with ibuprofen. Ibuprofen-treated animals did not exhibit any PMN influx into the lung. Blood gas analysis of all 72 h oxygen-exposed animals did not show any abnormal values, although analysis of dry/wet weight ratios and histopathological examinations indicated noncardiogenic edema formation. After 96 h of oxygen exposure, both ibuprofen-treated and untreated groups suffered from severe acidosis. Gross cytoplasmic edema and partial destruction of lung endothelium were also observed. Mortality was 50% after 96 h of oxygen exposure. Our study, thus, demonstrates that ibuprofen cannot prevent hyperoxic lung injury although it inhibits the influx of PMN into the injured lung, suggesting that PMN are not directly involved in the injury process.