EFFECT OF CALCITRIOL ON THE PRODUCTION OF T-CELL-DERIVED CYTOKINES INPSORIASIS

Although the use of vitamin D analogues in the treatment of psoriasis has been an important new development, the mechanisms of action of the se drugs are not fully understood, Psoriasis results from hyperprolife ration of keratinocytes, and various studies attribute a crucial role to the locally infiltrating T lymphocytes. In an attempt to add to the understanding of the mechanisms of calcitriol therapy, we determined the effect of this drug on T cells by studying its effect on prolifera tion and on the production of various cytokines by T-cell clones prepa red from psoriatic skin after non-specific activation with the combina tion of phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA), The addition of increasing doses (10(-9)-10(-5) mol/l) of calcitriol to these T cells resulted in a dose-dependent inhibition in lymphocyte proliferation and in production of the type 1 cytokines IFN-gamma and IL-2, the type 2 cytokines IL-4 and IL-5, The general cytoliines TNF- alpha and GM-CSF were not significantly inhibited. These data suggest that calcitriol is involved in the treatment of psoriasis via inhibiti on of the expansion, and cytokine production, of skin-infiltrating T l ymphocytes.