1,25-dihydroxyvitamin D-3 - a hormone with immunomodulatory properties

The active vitamin D metabolite, 1,25-dihydroxyvitamin DJ [1,25-(OH)(2)D-3] , exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secr etion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabo lite further inhibits class II antigen expression and enhances suppressor;a ctivity, In animal models of autoimmunity, 1,25-(OH)(2)D-3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diab etes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)(2)D-3 has led to an anti-prolifer ative effect in psoriasis, antineoplastic effect in prostate cancer, and im munomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D-3.