The effect of tacalcitol (1,24(OH)2D3) on cutaneous inflammation, epidermal proliferation and keratinization in psoriasis: a placebo-controlled, double-blind study.
The aim of the present study was to discover to what extent 1,24(OH)2D3 ointment (tacalcitol; 4 micrograms/g) can modulate epidermal proliferation and keratinization, and several aspects of inflammation. Ten patients with psoriasis vulgaris were included in a placebo-controlled, double-blind study, using 1,24(OH)2D3 ointment (4 micrograms/g). Before, and after 8 weeks of treatment, punch biopsies were taken from lesions treated with the active agent and placebo-treated lesions. An immunohistochemical study was carried out using monoclonal antibodies against the hyperproliferation-associated keratin 16, against cycling nuclei, filaggrin, involucrin, T lymphocytes, Langerhans cells, CD14 and polymorphonuclear leucocytes (PMN). The Wilcoxon test for matched pairs was used for statistical analysis of results. The biopsies from the lesions treated with the active agent showed a statistically significant change towards normalization of all aspects of inflammation studied, and of epidermal proliferation and keratinization, but there did not appear to be any effect on Langerhans cells. The only parameter which showed a significant alteration in the placebo-treated lesions was the number of cycling nuclei in the epidermis (P < or = 0.02). However, the biopsies from the plaques treated with the active agent showed a greater decrease of cycling cells (decrease: Mactive = 70, Mplacebo = 53) and a lower P-value (< or = 0.01). We therefore conclude that at the cell biological level 1,24(OH)2D3 ointment (4 micrograms/g) has a substantial effect on several cell types, with regard to inflammation, epidermal proliferation and keratinization, with the exception of Langerhans cells.
Gerritsen
M J
MJ
Department of Dermatology, University Hospital Nijmegen, The Netherlands.
Boezeman
J B
JB
van Vlijmen-Willems
I M
IM
Van de Kerkhof
P C
PC
D002455:Cell Division / Q000187:drug effects; D004100:Dihydroxycholecalciferols / Q000627:therapeutic use*; D004311:Double-Blind Method; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D000091344:Filaggrin Proteins; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy; D007633:Keratins / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D004100:Dihydroxycholecalciferols; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C023850:1 alpha,24-dihydroxyvitamin D3; D007633:Keratins