Cyclosporine A inhibits allergen-induced late asthmatic response and increase of airway hyperresponsiveness in guinea pigs

Abstract

Considerable interest has recently focused on the role of T-cell function in the pathogenesis of asthma. We have previously demonstrated that repeated inhaled antigen (ovalbumin; OA) exposure resulted in an appearance of late phase airway obstruction (LAR) in more than 50% and significant increase of airway hyperresponsiveness (AH) in guinea pig experimental models. We have studied the effect of cyclosporine A (CsA), a potent helper T-cell suppressant, on these models in vivo. Respiratory resistance (Rrs) of sensitized guinea pigs by repeated OA inhalation was measured by the oscillation method and AH estimated as an inhaled concentration of histamine, causing a 200% increase in the baseline Rrs (PC200 Hist). The magnitude of immediate OA (10 mg/ml/min) inhalation-induced bronchoconstriction was not significantly different in CsA-treated (25 mg/kg/day, 7-day oral administration) and non-treated groups. However, the development of LAR was markedly inhibited in CsA treatment groups (n = 5). Antigen-induced increase of AH at 24 hr and 5 days was also significantly inhibited by CsA pretreatment. We conclude that CsA is capable of inhibiting the development of LAR and increase of AH, and thus the regulation of T-cell function may contribute to the treatment of asthma.