title: Dose-dependent inhibition of allergic inflammation and bronchial hyperresponsiveness by budesonide in ovalbumin-sensitised Brown-Norway rats.
abstract: 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.
authors.affiliation: Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse St., London SW3 6LY, UK.
authors.forename: Sum Yee
authors.initials: SY
authors.lastname: Leung
authors.forename: Alison S
authors.initials: AS
authors.lastname: Williams
authors.forename: Puneeta
authors.initials: P
authors.lastname: Nath
authors.forename: Q Thai
authors.initials: QT
authors.lastname: Dinh
authors.forename: Timothy
authors.initials: T
authors.lastname: Oates
authors.forename: F-Xavier
authors.initials: FX
authors.lastname: Blanc
authors.forename: Paul R
authors.initials: PR
authors.lastname: Eynott
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
mesh_terms: 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
chemical_list: D005938:Glucocorticoids; D019819:Budesonide; D010047:Ovalbumin; D000109:Acetylcholine