CYCLOSPORINE-A REDUCES T-LYMPHOCYTE ACTIVITY AND IMPROVES AIRWAY HYPERRESPONSIVENESS IN CORTICOSTEROID-DEPENDENT CHRONIC SEVERE ASTHMA

Background: Although cyclosporine A is proving effective for chronic s evere asthma, its mechanism of action in this disease is unclear. Obje ctive: This open study was conducted to determine whether cyclosporine A therapy would reduce the degree of airway hyperresponsiveness and T Iymphocyte activity. Methods: After a 6-week run-in period, nine pati ents with corticosteroid-dependent chronic severe asthma were treated with cyclosporine A (initial dose 5 mg/kg per day) for 12 weeks. Resul ts: Weekly mean morning peak expiratory flow significantly increased i n six subjects during the last 6 weeks of trial. Geographic mean PC20- acetylcholine (the provocative concentration of acetylcholine required to cause a 20% fall in FEV(1)) was 0.147 mg/mL before cyclosporine A treatment and increased to 0.216 mg/mL at 6 weeks and to 0.379 mg/mL a t 12 weeks after treatment. The increase at 12 weeks was statistically significant (P < .05). The percentage of CD4-positive T lymphocytes b earing IL-2 receptor (a marker of T cell activation) in the peripheral blood decreased significantly at 6 weeks (P < .05), but returned to b aseline value at 12 weeks, probably due to cyclosporine A dose reducti on in seven subjects. Serum IgE levels and peripheral blood eosinophil counts, however, which are dependent on IL-4 and IL-5, respectively, were still significantly decreased at 12 weeks, suggesting lymphokine production remained suppressed even after cyclosporine A dose was redu ced. Conclusion: Taken together, these data suggest that cyclosporine A may act in asthma, at least in part, by inhibition of T lymphocyte a ctivation and by reducing the degree of airway hyperresponsiveness.