title: Dexamethasone treatment fails to reduce oxygen-induced lung injury in the preterm guinea pig. Effects on pulmonary inflammation and antioxidant status.
abstract: Dexamethasone (10 mg/kg/day) or vehicle was administered in a randomized, 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 further 96 hr. Treatment with dexamethasone had no effect on survival of preterm pups maintained in either 21% or 95% O2. Dexamethasone treatment 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% vs 100%, P < 0.05). Surviving pups developed acute lung injury, characterized 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 inflammatory cell infiltration, in particular neutrophils, both during oxygen exposure (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). Elastase activity in bronchoalveolar lavage fluid, which was primarily of neutrophil origin, was unchanged by dexamethasone treatment. Dexamethasone-treated pups had increased pulmonary antioxidant enzyme activities (Cu/Zn-superoxide dismutase; Mn-superoxide dismutase, catalase and glutathione peroxidase) during recovery from oxidative injury. Although there was both a marked reduction in numbers of neutrophils in the lung and elevated pulmonary antioxidant enzyme activities in dexamethasone-treated pups, the degree of microvascular permeability, as determined by both the lung wet weight/dry weight ratio and the presence of plasma proteins in the lavage fluid, was unchanged. Combined, these results 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.
authors.affiliation: Department of Human Nutrition, University of Southampton, U.K.
authors.forename: G I
authors.initials: GI
authors.lastname: Town
authors.forename: G J
authors.initials: GJ
authors.lastname: Phillips
authors.forename: M
authors.initials: M
authors.lastname: Landreau
authors.forename: J
authors.initials: J
authors.lastname: Louden
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: F J
authors.initials: FJ
authors.lastname: Kelly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000975:Antioxidants / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000382:microbiology; D003907:Dexamethasone / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000032:analysis; D006168:Guinea Pigs; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D008171:Lung Diseases / Q000139:chemically induced* / Q000401:mortality; D008833:Microcirculation / Q000187:drug effects; D008954:Models, Biological; D008969:Molecular Sequence Data; D010100:Oxygen / Q000633:toxicity*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010539:Permeability; D013482:Superoxide Dismutase / Q000032:analysis
chemical_list: D000975:Antioxidants; D003907:Dexamethasone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; D010100:Oxygen