Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system

Vitamin D is an important immune system regulator. The active form of vitamin D, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3], has been shown to inhibit the development of autoimmune diseases, including inflammatory bowel disease (IBD). Paradoxically, other immune system-mediated diseases (experimental asthma) and immunity to infectious organisms were unaffected by 1,25(OH)(2)D-3 treatment. There are similar paradoxical effects of vitamin D deficiency on various immune system functions. Vitamin D and vitamin D receptor (VDR) deficiency resulted in accelerated IBD. Experimental asthma was unaffected by 1,25(OH)(2)D-3 treatment and was less severe among VDR-deficient mice. Vitamin D is a selective regulator of the immune system, and the outcome of 1,25(OH)(2)D-3 treatment, vitamin D deficiency, or VDR deficiency depends on the nature of the immune response (eg, infectious disease, asthma, or autoimmune disease). An additional factor that determines the effect of vitamin D status on immune function is dietary calcium. Dietary calcium has independent effects on IBD severity. Vitamin D-deficient mice on low-calcium diets developed the most severe IBD, and 1,25(OH)(2)D-3 treatment of mice on low-calcium diets improved IBD symptoms. However, the best results for IBD were observed when the calcium concentration was high and 1,25(OH)(2)D-3 was administered. Both the type of immune response and the calcium status of the host determine the effects of vitamin D status and 1,25(OH)(2)D-3 on immunity.