Clinical response to cyclosporin in chronic severe asthma is associated with reduction in serum soluble interleukin-2 receptor concentrations.
Activated T-lymphocytes play an important role in asthma pathogenesis and release soluble interleukin-2 receptor (sIL-2R), which can be detected in the serum. In a recent randomized, cross-over trial we showed that cyclosporin, an inhibitor of T-lymphocyte activation, improved lung function in patients with chronic severe asthma. To investigate whether changes in serum sIL-2R concentration could be related to clinical response we prospectively compared serum sIL-2R concentrations in patients during cyclosporin and placebo treatment. Peripheral venous blood was obtained from 22 patients during the last 4 weeks of both the cyclosporin and placebo treatment periods and serum stored at -80 degrees C pending measurement of sIL-2R concentration by enzyme immunoassay. Soluble IL-2R was detected in all samples at a concentration range of 191-2,297 U.ml-1. Mean serum concentrations of sIL-2R were significantly lower on cyclosporin therapy (560 U.ml-1) as compared with placebo (676 U.ml-1). The decreases in serum sIL-2R concentrations associated with cyclosporin therapy in these patients correlated with the percentage increases in their morning peak expiratory flow rate (PEFR) measurements on cyclosporin as compared with placebo. These data demonstrate that in patients with chronic severe asthma, cyclosporin therapy which results in clinical improvement is associated with a decrease in serum concentrations of sIL-2R. This is compatible with the hypothesis that cyclosporin ameliorates asthma, at least partly, by inhibition of T-lymphocyte activation.
Alexander
A G
AG
Dept of Allergy and Clinical Immunology, National Heart & Lung Institute, London, UK.
Barnes
N C
NC
Kay
A B
AB
Corrigan
C J
CJ
D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010366:Peak Expiratory Flow Rate; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013601:T-Lymphocytes / Q000187:drug effects
D015375:Receptors, Interleukin-2; D016572:Cyclosporine