Allergen-induced bronchial eosinophilia in guinea-pigs is inhibited by both pre- and post-induction cyclosporin-A treatments

Repeated treatment of sensitized guinea-pigs with cyclosporin-A (CS-A) before aerosol allergen challenge is known to inhibit the subsequent bronchial eosinophilia, It is not known, however, if the drug is also effective on established/on-going bronchial eosinophilia, We have, therefore, studied the effect of CS-A on allergen-induced eosinophil recruitment into the bronchoalveolar lavage (BAL) fluid of guinea-pigs when given before or after induction. Ovalbumin-immunized guinea-pigs were treated with CS-A (20 mg/kg subcutaneously) or vehicle daily for varying periods before a single aerosol allergen challenge. In animals in which bronchial eosinophilia was maintained with repeated aerosol allergen challenge, CS-A or vehicle was given daily for varying periods after the first allergen challenge. BAL and cell count were performed 24 h after the last challenge. In vehicle-treated animals, a single allergen challenge caused a 4-5 fold increase in the number of eosinophils in the BAL fluid after 24 h, declining to baseline by 7 days. In repeatedly-challenged animals, this response was sustained throughout. Eosinophil infiltration was significantly inhibited when CS-A was given daily for 7-14 days, but not for 1 or 3 days, before allergen challenge. When given during an established/on-going eosinophil infiltration, a significant inhibition was seen after administration for 5 or 7 days, but not for 1 or 3 days. These results show that repeated CS-A administration inhibits not only the induction of allergic bronchial eosinophilia but also the maintenance of an established one. This may be relevant in the treatment of allergic diseases, such as asthma, in which drug administration often begins when eosinophilia is already established. (C) 2000 International Society for Immunopharmacology. Published by Elsevier Science Ltd. All rights reserved.