CLEARING OF PSORIASIS BY A NOVEL IMMUNOSUPPRESSIVE MACROLIDE

Accumulating evidence suggests that psoriasis may be a genetically det ermined immunogenic, inflammatory disorder based on an ongoing autorea ctive Th-1 response, Systemic immunosuppressive therapy is highly effe ctive but fraught with longterm side effects, Our research therefore f ocuses on therapeutic strategies that induce local immunosuppression i n the skin by topical, transepidermal delivery of immunosuppressive dr ugs, SDZ 281-240 is a newly developed macrolide of the ascomycin type, It is immunosuppressive by a mechnism of action similar to that of FK 506 but has no antiproliferative activity against keratinocytes in vit ro. To evaluate whether SDZ 281-240 exhibits antipsoriatic activity wh en applied topically, we tested 15 patients with severe, recalcitrant psoriasis, using a microplaque assay in a randomized, double-blind, pl acebo-controlled study, comparing the therapeutic efficacy of the macr olide with a potent halogenated corticosteroid and vehicle, All patien ts showed a significant improvement of psoriatic lesions treated with two concentrations of the macrolide and, as expected, with the cortico steroid but not with placebo, Both concentrations of the macrolide led to clearing of psoriasis after 10 days of treatment and biopsies conf irmed a reversal of the histopathological and immunopathological pheno type of psoriasis to that of normal skin, Thus, an immunosuppressive a gent that interferes with early T cell activation can be designed to p enetrate into psoriatic lesions when applied topically and to be funct ionally active within the skin to suppress the ongoing psoriatic proce ss.