The clinical efficacy and tolerability of the
vitamin D3 analogues
calcitriol,
calcipotriol and 1 alpha, 24 dihydroxyvitamin D3 in the treatment of
psoriasis have been assessed in various clinical studies. In vitro and in vivo investigations have shown interference of these compounds with epidermal growth, keratinisation and
inflammation. In this study we quantified the in vivo cell biological effects during treatment of psoriatic plaques with 1 alpha, 24 dihydroxyvitamin D3. By using a flow cytometric triple labelling procedure, we could discriminate different epidermal subpopulations, permitting precise assessment of epidermal cell cycle kinetics. Twenty patients with plaque-type
psoriasis were treated in a double-blind placebo-controlled left-right comparative study with 1 alpha, 24 dihydroxyvitamin D3
ointment (4 micrograms/g applied once daily) for 8 weeks. Epidermal cell
suspensions prepared from keratotome biopsies taken before and
after treatment were stained with
TO-PRO-3 iodide (a new
DNA fluorochrome) and
monoclonal antibodies against
keratin 10 (as a marker for differentiation) and
vimentin (as a marker for
inflammation), simultaneously. The flow cytometric analyses showed a significant decrease of proliferating basal keratinocytes in verum-treated lesions, whereas such a decrease was not observed in placebo-treated lesions. The amount of
keratin 10-positive keratinocytes increased and the presence of
vimentin-positive cells decreased in cell
suspensions derived from both verum- and placebo-treated lesions, but these effects were not significant. We conclude that multiparameter flow cytometry promises to be an adequate approach to assess the interference of antipsoriatic treatments with cutaneous
inflammation, epidermal proliferation and keratinisation. Topical 1 alpha, 24 dihydroxyvitamin D3 seems to exert its in vivo antipsoriatic effect mainly through an inhibition of epidermal growth.