Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats

Am Rev Respir Dis. 1992 Jun;145(6):1289-94. doi: 10.1164/ajrccm/145.6.1289.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Aerosols
  • Animals
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / pathology
  • Cyclosporine / pharmacology*
  • Dexamethasone / pharmacology*
  • Eosinophils / immunology*
  • Immunization
  • Lymphocyte Activation / drug effects
  • Male
  • Ovalbumin / immunology*
  • Rats
  • Rats, Inbred BN
  • T-Lymphocytes / immunology*

Substances

  • Aerosols
  • Dexamethasone
  • Cyclosporine
  • Ovalbumin
  • Acetylcholine