In vivo dexamethasone effects on neutrophil effector functions in a rat model of acute lung injury.
Glucocorticoids, while potent antiinflammatory agents, have not been proven to be efficacious in Acute Respiratory Distress Syndrome, ARDS. Previous studies from this laboratory have reported that dexamethasone pretreatment of rats resulted in a 40-60% reduction in neutrophil influx into the airways following intratracheal administration of lipopolysaccharide, LPS. In the present study, the in vivo effects of dexamethasone on BAL neutrophil effector functions were evaluated by flow cytometry. BAL neutrophils from rats pretreated with dexamethasone (20 mg/kg, i.p. at 2 h before and 8 h after LPS) and harvested 20 h after LPS challenge demonstrated a 35% reduction in their ability to undergo an ex vivo oxidative burst with phorbol myristate acetate. This modest reduction in the oxidative burst was not related to a more general suppression of neutrophil effector functions as neither phagocytosis of opsonized bacteria nor expression of the beta-2 integrins CD11a and CD11b were similarly inhibited. Therefore, the neutrophil population which has migrated into the airways in dexamethasone pretreated rats retains the capacity to mediate host defense but also to exacerbate inflammation associated tissue damage.
O'Leary
E C
EC
Department of Cardiovascular Research, Lilly Research Labs, Eli Lilly and Co., Indianapolis, Indiana 46285, USA.
Evans
G F
GF
Zuckerman
S H
SH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D003907:Dexamethasone