Infants and adults on
oxygen often are treated with
glucocorticoids in an attempt to reduce lung inflammatory injury. However,
glucocorticoids hasten the development of hyperoxic
lung injury in some animal models. The purpose of this study was to test the hypothesis that
dexamethasone alters the lung inflammatory responses to
hyperoxia exposure. We studied male Sprague-Dawley rats, placing them in >95%
oxygen immediately after administration of 0, 0.1, 1, or 10 mg/kg of
dexamethasone. At 0, 24, or 48 hr of exposure to
hyperoxia, extravascular lung water contents were measured, and lung inflammatory responses were assessed by lung
myeloperoxidase activities, lung neutrophil counts, and lung expression of
E-Selectin and intercellular adhesions molecule-1 (ICAM-1).
Dexamethasone, independent of exposure to
hyperoxia, led to marked increases in lung neutrophil counts, without increases in lung
myeloperoxidase activities or increases in the expression of the adhesion molecules.
Hyperoxia exposure also enhanced lung neutrophil accumulation, and extravascular lung water increased earlier in animals exposed to
hyperoxia and
dexamethasone than in those exposed to
hyperoxia alone. In conclusion, the increase in lung neutrophils in
dexamethasone-treated rats without enhanced expression of
E-Selectin or intracellular adhesions molecule-1 suggests that
dexamethasone leads to lung neutrophil accumulation by its effect on neutrophils. The more rapid development of hyperoxic
lung injury associated with earlier lung neutrophil accumulation suggests that
dexamethasone-induced lung neutrophil sequestration primes the lung for the development of hyperoxic
lung injury and supports further the conclusion that
lung inflammation contributes significantly to the development of hyperoxic
lung injury.