Effects of budesonide on airway hyperreactivity and inflammatory response in a rat model of allergic asthma
Airway hyperreactivity and inflammatory response provoked by ovalbumin (OA) exposure and effects of corticosteroid pretreatment were studied in OA-sensitized Brown Norway rats. Male 9-week-old Brown Norway rats were sensitized with OA, alum and Bordetella pertussis. Two weeks after sensitization, the animals were challenged with OA aerosols during simultaneous recording of lung function (using a novel dose control system which processes data on respiratory minute volume and aerosol concentration). One group was pretreated with 3 mg budesonide (BUD) intratracheally 18-24 h before challenge. A positive control (POS) group and the BUD group were challenged with OA, a negative control (NEG) group was exposed to the vehicle. Airway hyperreactivity was assessed by acetylcholine provocation 24 h after challenge (ED150=inhalational dose causing 150 % increase in lung resistance). 48 h after challenge, bronchoalveolar lavage (BAL) was performed and blood withdrawn for IgE analysis. A significa nt hyperreactivity was found in the POS versus NEG animals 24 h after challenge (ED150=3.0 +- 0.2 vs 7.3 +- 0.7 µg ACh, mean +- SEM). No hyperreactivity was detected in the BUD group (6.8 +- 0.6). Correlating with this, significant eosinophillia and increase in total protein and LDH were detected in lung lavage fluid in the POS group but not in the BUD group versus the NEG group 48 h after OA challenge (POS, NEG, BUD: Eos.: 45 +-4, 10 +-3, 11 +-2 %; TP: 1309 +- 182, 326 +- 46, 219 +- 16 mg/l; LDH: 122 +- 17, 52 +- 4, 43 +- 3 U/l). We conclude: budesonide pretreatment 18-24 h before antigen challenge almost completely blocks airway hyperreactivity as well as inflammatory response after antigen challenge in a rat model for allergic asthma.