The immunomodulatory drugs cyclosporin A, mycophenolate mofetil, and sirolimus (rapamycin) inhibit allergen-induced proliferation and IL-5 production by PBMCs from atopic asthmatic patients.
We have used an optimized, physiologically relevant in vitro assay system to show that in a concentration-dependent fashion the immunomodulatory drugs cyclosporin A, mycophenolate mofetil, and sirolimus (rapamycin), as well as the glucocorticoid dexamethasone, inhibit allergen-driven T-cell proliferation and IL-5 production in PBMCs from allergen-sensitized atopic asthmatic individuals at physiologic concentrations. This effect of cyclosporin A might at least partially account for its established clinical efficacy in sparing systemic glucocorticoid therapy while improving lung function in chronic, severe, glucocorticoid-dependent asthma. The data are also compatible with the hypothesis that the newer immunomodulatory drugs mycophenolate mofetil and sirolimus exert similar effects, perhaps with a more favorable benefit/risk ratio.
Powell
N
N
Department of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
Till
S
S
Bungre
J
J
Corrigan
C
C
D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020123:Sirolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D015848:Interleukin-5; D003907:Dexamethasone; D016572:Cyclosporine; D009173:Mycophenolic Acid; D020123:Sirolimus