Effect of dexamethasone on airway inflammation and responsiveness after antigen challenge of the rat.
The purpose of this study was to examine the effects of dexamethasone on airway responsiveness and lung inflammation of rats at 8 h, 32 h, and 7 d after allergen challenge. Brown-Norway male rats, 7 to 8 wk old, were actively sensitized to ovalbumin (OA) and challenged 14 d later. The rats were divided into a control group (n = 31) and a test group (n = 34) that received dexamethasone (DEXA) (0.3 mg/kg intraperitoneally) 14 h and 2 h before saline or OA challenge. For challenge, rats were anesthetized with pentobarbital and intubated endotracheally. Aerosols of OA (5% wt/vol in saline) were administered for 5 min. Responsiveness to inhaled aerosols of methacholine and the total and differential leukocyte counts in the large airways (generations 0 to 5), small airways, and parenchyma isolated by tissue mincing and digestion were measured at 8 h, 32 h, and 7 d after OA challenge. The cellular influx into the airways and parenchyma was highest at 8 h and decreased progressively over 7 d. DEXA significantly inhibited the cellular influx after allergen challenge. At 8 h, cellular return from the large airways was 3.61 +/- 0.5 x 10(6) (controls) versus 1.0 +/- 0.2 x 10(6) (DEXA), and from the small airways and parenchyma was 31.7 +/- 2.8 x 10(6) (controls) versus 21.9 +/- 2.9 x 10(6) (DEXA) (p < 0.05). The differences were attributable mostly to decreases in neutrophils in DEXA-treated animals. In control animals, neutrophil yield fell between 8 and 32 h, whereas eosinophils and 32 h, whereas eosinophil and lymphocyte counts increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Renzi
P M
PM
Respiratory Health Network of Centres of Excellence, André Viallet Research Institute, St-Luc Hospital, University of Montreal, Quebec, Canada.
Olivenstein
R
R
Martin
J G
JG
D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D001991:Bronchitis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D007114:Immunization; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000336:Aerosols; D000485:Allergens; D000941:Antigens; D016210:Methacholine Chloride; D003907:Dexamethasone