Tacrolimus suppressed the production of cytokines involved in atopic dermatitis by direct stimulation of human PBMC system. (Comparison with steroids)

Tacrolimus (FK506) ointment showed remarkable efficacy against atopic derma titis in animal models and clinical trials. The suppressive effect of tacro limus on the production of the cytokines involved in atopic dermatitis (IL- 2, IL-3, IL-4, IL-5, IFN-gamma and GM-CSF) from human peripheral blood mono nuclear cells (PBMC) was investigated. We constructed a new cytokine produc tion system in which T cells are activated by direct stimulation in vitro w ith anti-CD3/CD2 or anti-CD3/CD28 antibody combination. Tacrolimus inhibite d the production of these cytokines by both stimulations. In a comparative study with steroids (alclometasone dipropionate and betamethason valerate) in anti-CD3/CD2 system, tacrolimus and both steroids inhibited Th1 cytokine s (IL-2, IFN-gamma:),Th3, cytokines (IL-4, IL-5) and IL3,GM-CSF (produced b y both Th1 and Th2). The suppressive effect of tacrolimus on cytokine produ ction was stronger than that of alclometasone dipropionate and equal to or stronger than that of betamethason valerate. The effective dose of tacrolim us (IC50, 0.02-0.11 ng/ml) is almost the same as for Th1 and Th2 cytokines, and 1 ng/ml of tacrolimus suppressed all cytokines completely. These resul ts suggest that tacrolimus suppresses the allergic cytokines from T cells, and that tacrolimus ointment is effective against atopic dermatitis through the inhibition of cytokine production. (C) 2001 Elsevier Science B.V. All rights reserved.