Dose-dependent inhibition of allergic inflammation and bronchial hyperresponsiveness by budesonide in ovalbumin-sensitised Brown-Norway rats

Pulm Pharmacol Ther. 2008;21(1):98-104. doi: 10.1016/j.pupt.2007.01.001. Epub 2007 Jan 25.

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.

MeSH terms

  • Acetylcholine / adverse effects
  • Animals
  • Blood Cell Count
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / prevention & control*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / cytology
  • Budesonide / administration & dosage
  • Budesonide / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use*
  • Hypersensitivity / immunology
  • Hypersensitivity / prevention & control*
  • Male
  • Ovalbumin / immunology
  • Rats

Substances

  • Glucocorticoids
  • Budesonide
  • Ovalbumin
  • Acetylcholine