Can clinical response to cyclosporin in chronic severe asthma be predicted by an in vitro T-lymphocyte proliferation assay?
This study tests the hypothesis that the clinical response to cyclosporin therapy of patients with chronic severe asthma is related to the sensitivity of their T-lymphocytes to the antiproliferative effects of cyclosporin in vitro. In a previous study, we observed such a relationship with glucocorticoids and the same lectin-driven proliferation assay was used in the present study. Peripheral blood mononuclear cells were obtained from 33 patients participating in a cross-over trial of oral cyclosporin therapy during both cyclosporin and placebo treatment periods, and cultured in the presence of phytohaemagglutinin and serial dilutions of cyclosporin and dexamethasone. Proliferation was measured by tritiated thymidine uptake. Both cyclosporin and dexamethasone inhibited T-lymphocyte proliferation in a concentration-dependent manner in vitro at concentrations encompassing those achieved in peripheral blood during therapy in vivo. T-lymphocytes from the asthmatic patients showed a range of sensitivity to the antiproliferative effects of cyclosporin, but this could not be correlated with improvements in peak expiratory flow rate (PEFR) or forced expiratory volume in one second (FEV1) during cyclosporin therapy as compared with placebo. In contrast to previous observations with glucocorticoids, this in vitro T-lymphocyte proliferation assay is not predictive of clinical response to cyclosporin therapy in chronic severe asthmatics.
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 / Q000188:drug therapy* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
D010835:Phytohemagglutinins; D003907:Dexamethasone; D016572:Cyclosporine