Topical vitamin D3 derivatives impair the epidermal permeability barrier in normal mouse skin.

Abstract

Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin. The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo. Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed. A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization. These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.