TREATMENT WITH CYCLOSPORINE-A DURING SENSITIZATION WITH TRIMELLITIC ANHYDRIDE ATTENUATES THE AIRWAY RESPONSES TO ALLERGEN CHALLENGE 3 WEEKS LATER

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 mu l) 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.