DEXAMETHASONE TREATMENT FAILS TO REDUCE OXYGEN-INDUCED LUNG INJURY INTHE PRETERM GUINEA-PIG - EFFECTS ON PULMONARY INFLAMMATION AND ANTIOXIDANT STATUS

Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomiz ed. controlled fashion to 3-day preterm guinea pigs exposed to either 21% oxygen or 95% oxygen for 72 hr and maintained in room air for a fu rther 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatm ent reduced the growth rate of pups, the effect occurring earlier (0-3 days) in 21% O2-treated pups than in 95% O2-treated pups (5-7 days). Exposure to 95% O2 reduced the survival rate of preterm animals (73% v s 100% P < 0.05). Surviving pups developed acute lung injury, characte rized by the accumulation of a protein-rich exudate in the alveoli and an infiltration of inflammatory cells, particularly neutrophils into the lung. Dexamethasone treatment attenuated the pulmonary inflammator y cell infiltration, in particular neutrophils, both during oxygen exp osure (16.4 x 10(4) vs 9.4 x 10(4)/mL; P < 0.05) and following return to ambient conditions (28.0 x 10(4) vs 5.1 x 10(4)/mL; P < 0.05). Elas tase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexametha sone-treated pups had increased pulmonary antioxidant enzyme activitie s (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and g lutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reductio[i in numbers of neutrophils in the l ung and elevated pulmonary antioxidant enzyme activities in dexamethas one-treated pups. the degree of microvascular permeability, as determi ned by both the lung wet weight/dry weight ratio and the presence of p lasma proteins in the lavage fluid, was unchanged. Combined, these res ults imply that dexamethasone, although capable of blunting the influx of neutrophils to the hyperoxia-exposed lung and inducing antioxidant defences in the immature lung, cannot modify the progression of acute oxygen-induced injury of the immature lung.