Temporal profile of forced expiratory lung function in allergen-challenged Brown-Norway rats

The Brown-Norway rat is often used to study the allergic pulmonary response. However, relatively little is known about the delayed phase reactions after allergen challenge in this species. To evaluate the temporal changes in lung function and elucidate the mechanisms involved in the delayed phase response, Brown-Norway rats were sensitized and challenged to aerosolized ovalbumin and lung functions were measured by forced expiratory maneuvers and forced oscillation for up to 10 days after a single antigen challenge. Statistically significant (P < 0.05) reductions in inspiratory capacity, forced vital capacity, functional residual capacity, peak expiratory flow and maximum mid-expiratory flow and increases in respiratory system resistance and elastance were seen by I to 3 days after ovalbumin challenge that returned to baseline by 10 days. The reductions in lung function after ovalbumin challenge were blocked by the corticosteroid, betamethasone (1 mg/kg, p.o.). Histological evaluation of lung tissue of sensitized rats demonstrated evidence of interstitial pulmonary edema, an increase in tissue eosinophils and an increase in Periodic Acid Schiff-positive cells in the airway epithelium. Bronchoalveolar lavage fluid samples showed large numbers of eosinophils and increased mucin content up to 6 days after antigen challenge. There was also an increase in wet-to-dry lung weight ratio in the lungs of sensitized rats after antigen. These results demonstrate that prolonged reductions in lung function occur after a single antigen challenge in Brown-Norway rats that is probably due to inflammatory processes producing interstitial pulmonary edema, mucus secretion and cellular influx into the lungs. (c) 2006 Elsevier B.V All rights reserved.