Dose-dependent inhibition of allergic inflammation and bronchial hyperresponsiveness by budesonide in ovalbumin-sensitised Brown-Norway rats.
Corticosteroids are known to inhibit bronchial hyperresponsiveness (BHR) and allergic inflammation but there is little information on its dose-dependence. We examined the effect of different doses of the glucocorticosteroid budesonide in an allergic model. Brown-Norway rats were sensitised to ovalbumin (OVA) and pretreated with an intra-gastric dose of budesonide (0.1, 1.0, or 10 mgkg(-1)). Exposure to OVA induced BHR, accumulation of eosinophils in the bronchoalveolar lavage (BAL) fluid and in the airways submucosa. Budesonide dose-dependently inhibited BAL fluid influx of lymphocytes, eosinophils and neutrophils, tissue eosinophils and lymphocytes and BHR. At 0.1 mgkg(-1), budesonide did not inhibit these parameters but at 1 mgkg(-1), BAL fluid eosinophils and T-cells, and submucosal T-cells were significantly reduced. At 10 mgkg(-1), budesonide suppressed BHR, BAL fluid inflammatory cells numbers and tissue eosinophilia. T-cell numbers were more related to BHR than eosinophil numbers. Budesonide inhibited both airway inflammation and BHR, but BAL fluid eosinophil cell counts may be dissociated from BHR.
Leung
Sum Yee
SY
Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse St., London SW3 6LY, UK.
Williams
Alison S
AS
Nath
Puneeta
P
Dinh
Q Thai
QT
Oates
Timothy
T
Blanc
F-Xavier
FX
Eynott
Paul R
PR
Chung
Kian Fan
KF
D000109:Acetylcholine / Q000009:adverse effects; D000818:Animals; D001772:Blood Cell Count; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019819:Budesonide / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats
D005938:Glucocorticoids; D019819:Budesonide; D010047:Ovalbumin; D000109:Acetylcholine