In Vivo Upregulation of Interleukin-4 Is One Mechanism Underlying the Immunoregulatory Effects of 1,25-Dihydroxyvitamin D3

The active form of vitamin D (1,25-(OH)2D3) is a potent immune system regulator. In vivo the oral administration of 1,25-(OH)2D3 completely prevents experimental autoimmune encephalomyelitis (EAE), significantly prolongs allograft survival, and prevents collagen-induced arthritis. 1,25-(OH)2D3 given to mice increased IL-4 protein and transcript levels. We have now tested the efficacy of 1,25-(OH)2D3 on EAE development and allograft survival in IL-4-deficient [knockout (ko)] mice. 1,25-(OH)2D3 was found to be much less effective in the absence of IL-4, suggesting that IL-4 production is a significant factor in the action of 1,25-(OH)2D3 on the immune system.