Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats.
We studied the effects of dexamethasone and cyclosporin A on the airway hyperresponsiveness (AHR) and the influx of inflammatory cells into the bronchoalveolar lavage (BAL) fluid seen 18 to 24 hr after exposure to aerosolized ovalbumin in actively ovalbumin-sensitized Brown-Norway rats. Allergen exposure resulted in an approximately sevenfold increase in bronchial responsiveness to inhaled acetylcholine associated with a significant increase in eosinophils and lymphocytes in BAL fluid. Dexamethasone (0.5 mg/kg administered intraperitoneally for 3 days) abolished the AHR and the increase in eosinophil and lymphocyte counts. However, cyclosporin A at two doses (5 and 50 mg given orally for 5 days) did not significantly prevent the induction of AHR while producing a significant inhibition of the eosinophil and lymphocyte influx. Dexamethasone (0.5 mg/kg for 3 days) or cyclosporin A (5 mg/kg for 5 days) on their own had no effect on airway responsiveness. We conclude that specific inhibition of T-lymphocyte activation in this Brown-Norway rat model is not sufficient to inhibit the induction of AHR despite suppressing allergen-induced eosinophilia in BAL fluid. However, corticosteroids, which have inhibitory effects on a wider range of inflammatory cells, are more effective. Our observations are in line with the potent effect of corticosteroids in airway inflammatory conditions such as asthma.
Elwood
W
W
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
Lötvall
J O
JO
Barnes
P J
PJ
Chung
K F
KF
D000109:Acetylcholine; D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000473:pathology; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004804:Eosinophils / Q000276:immunology*; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010047:Ovalbumin / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D013601:T-Lymphocytes / Q000276:immunology*
D000336:Aerosols; D003907:Dexamethasone; D016572:Cyclosporine; D010047:Ovalbumin; D000109:Acetylcholine