Skin immune dowregulators: from bench to bedside.

New generations of topical skin immune downregulators (SIDRs) were recently introduced as an alternative to glucocorticoids for the topical treatment of some inflammatory dermatoses. Tacrolimus, pimecrolimus, sirolimus and dunaimycins inhibit the transcription of proinflammatory cytokine genes through binding to specific immunophilins. Taken together, SIDRs are able to inhibit a number of pro-inflammatory mediator systems and inflammatory cells with major importance for several cutaneous dermatitides. Therefore this group of compounds targeted dermatological diseases from the beginning of drug development. Several clinical trials have demonstrated the efficacy of tacrolimus and pimecrolimus in treating moderate to severe atopic dermatitis. Psoriasis, contact dermatitis and other dermatoses could also be indications for SIDRs. This review presents the cell biology changes and the mode of action of SIDRs. Their pharmacokinetics, clinical results and site effects are compared.