Treatment with cyclosporin A during sensitization with trimellitic anhydride attenuates the airway responses to allergen challenge three weeks later

Abstract

The present studies examined the effects of oral treatment with cyclosporin A, betamethasone or azelastine administered over the time of sensitization with trimellitic anhydride on allergen-induced airway responses, compared to those of control animals given corn oil alone. Drugs were given for 8 days. The animals were sensitized with trimellitic anhydride (0.1 ml of 0.3% w/v) in corn oil given intradermally on days 4 and 5 of drug treatment. Three to four weeks after sensitization with free trimellitic anhydride, the animals were anesthetized, tracheostomized and challenged with trimellitic anhydride conjugated to guinea pig serum albumin (trimellitic anhydride-guinea pig serum albumin; 0.5%;50 μl) instilled via the airway route. In the same animal, we measured both lung resistance (R l ) to monitor airflow obstruction, and extravasation of Evans Blue dye (20 mg/kg) to quantify airway plasma exudation. In control animals, instillation of trimellitic anhydride-guinea pig serum albumin into the tracheal lumen caused a slowly progressing increase in R l over the observation period (6 min), in addition to extravasation of Evans Blue dye at all airway levels. In animals treated with 50 mg/kg of cyclosporin A, both the allergen-induced increase in R l and extravasation of Evans Blue dye in intrapulmonary airways were significantly attenuated. However, neither betamethasone nor azelastine significantly affected these responses. We conclude that cyclosporin A may influence the immune system in the guinea pig during the induction of allergy, thus leading to attenuation of allergen-induced airway obstruction at later time points.