In vivo upregulation of interleukin-4 is one mechanism underlying the immunoregulatory effects of 1,25-dihydroxyvitamin D-3

The active form of vitamin D (1,25-(OH)(2)D-3) is a potent immune system re gulator. In vivo the oral administration of 1,25-(OH)(2)D-3 completely prev ents experimental autoimmune encephalomyelitis (EAE), significantly prolong s allograft survival, and prevents collagen-induced arthritis. 1,25-(OH)(2) D-3 given to mice increased IL-4 protein and transcript levels. We have now tested the efficacy of 1,25-(OH)(2)D-3 on EAE development and allograft su rvival in IL-4-deficient [knockout (ko)] mice. 1,25-(OH)(2)D-3 was found to be much less effective in the absence of IL-4, suggesting that IL-4 produc tion is a significant factor in the action of 1,25-(OH)(2)D-3 on the immune system. (C) 2000 Academic Press.