The action of a novel vitamin D₃ analogue, OCT, on immunomodulatory function of keratinocytes and lymphocytes

Abstract Topical vitamin D₃ has relatively recently been introduced for the treatment of psoriasis. Synthetic vitamin D₃ analogues with a high potential for inducing differentiation of cells, but with a low hypercalcemic effect have recently been developed. One such synthetic analogue of 1,25-dihydroxyvitamin D₃ (calcitriol), 22-oxacalcitriol (OCT), is a novel agent for the topical treatment of psoriasis. The activity of OCT in vitro was investigated and compared with that of a series of vitamin D₃ analogues as to their ability to inhibit murine T lymphocyte proliferation stimulated by con-A, to suppress IL-6 and IL-8 production by keratinocytes stimulated with IL-1α and TNFα, and to inhibit AP-1- and NFκB-dependent reporter gene expression. OCT inhibited the proliferation of lymphocytes and suppressed IL-8 and IL-6 production by keratinocytes to the same extent as the other vitamin D₃ analogues. It also inhibited AP-1- and NFκB-controlled luciferase activity to the same extent as the other vitamin D₃ analogues, which demonstrates its mechanism of action in the suppression of inflammatory processes.