TOPICAL TREATMENT OF PSORIATIC PLAQUES WITH 1-ALPHA-2,4 DIHYDROXYVITAMIN D-3 - A MULTIPARAMETER FLOW CYTOMETRIC ANALYSIS OF EPIDERMAL GROWTH, DIFFERENTIATION AND INFLAMMATION

The clinical efficacy and tolerability of the vitamin D-3 analogues ca lcitriol, calcipotriol and 1 alpha,24 dihydroxyvitamin D-3 in the trea tment of psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these comp ounds with epidermal growth, keratinisation and inflammation. In this study we quantified the in vivo cell biological effects during treatme nt of psoriatic plaques with 1 alpha,24 dihydroxyvitamin D-3. By using a flow cytometric triple labelling procedure, we could discriminate d ifferent epidermal subpopulations, permitting precise assessment of ep idermal cell cycle kinetics. Twenty patients with plaque-type psoriasi s were treated in a double-blind placebo-controlled left-right compara tive study with 1 alpha,24 dihydroxyvitamin D-3 ointment (4 mu g/g app lied once daily) for 8 weeks. Epidermal cell suspensions prepared from keratotome biopsies taken before and after treatment were stained wit h TO-PRO-3 iodide (a new DNA fluorochrome) and monoclonal antibodies a gainst keratin 10 (as a marker for differentiation) and vimentin (as a marker for inflammation), simultaneously. The flow cytometric analyse s showed a significant decrease of proliferating basal keratinocytes i n verum-treated lesions, whereas such a decrease was not observed in p lacebo-treated lesions. The amount of keratin 10-positive keratinocyte s increased and the presence of vimentin-positive cells decreased in c ell suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparamete r flow cytometry promises to be an adequate approach to assess the int erference of antipsoriatic treatments with cutaneous inflammation, epi dermal proliferation and keratinisation. Topical 1 alpha,24 dihydroxyv itamin D-3 seems to exert its in vivo antipsoriatic effect mainly thro ugh an inhibition of epidermal growth.