D-hormone and the immune system.

D-hormone [1,25(OH)2 D3] is an important immune system regulator that has been shown to inhibit development of autoimmune diseases including experimental inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), and type 1 diabetes. Paradoxically, other immune mediated diseases (experimental asthma) and immunity to infectious organisms were not found to be affected by D-hormone treatment. The effectiveness of D-hormone treatment of autoimmune diseases is due to inhibition of the development and function of Th1 cells and the induction of other Th cells including Th2 cells.

Calcium and 1 alpha,25-dihydroxyvitamin D3 target the TNF-alpha pathway to suppress experimental inflammatory bowel disease.

Vitamin D-deficient IL-10 knockout (KO) mice develop accelerated inflammatory bowel disease (IBD). Removing dietary calcium from the diets of vitamin D-deficient IL-10 KO mice increased the severity of IBD. The mice fed either calcium or active vitamin D (1 alpha,25-dihydroxyvitamin D3, 1,25D3), developed an intermediate form of IBD, while the mice fed both calcium and 1,25D3 had the mildest form of IBD.

Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence.

Low vitamin D status has been implicated in the etiology of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The optimal level of vitamin D intake required to support optimal immune function is not known but is likely to be at least that required for healthy bones. Experimentally, vitamin D deficiency results in the increased incidence of autoimmune disease.

Vitamin D receptor-deficient mice fail to develop experimental allergic asthma.

The active metabolite of vitamin D (1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))) is known to modulate the immune response in Th1 cell-directed diseases. To investigate the role of vitamin D in Th2 cell-directed diseases, experimental allergic asthma was induced in vitamin D receptor (VDR) knockout and in wild-type (WT) mice. As expected, WT mice developed symptoms of airway inflammation with an influx of eosinophils, elevated Th2 cytokine levels, mucous production, and airway hyperresponsiveness.

The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells.

Vitamin D is a potent immune system regulator. The active form of vitamin D (1,25(OH)(2)D(3)) suppresses the development of animal models of human autoimmune diseases. 1,25(OH)(2)D(3) decreased the proliferation of all T helper (h) cells and decreased the production of IFN-gamma, IL-2, and IL-5.

Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system.

Interleukin (IL)-2 knockout (KO) mice, which spontaneously develop symptoms of inflammatory bowel disease similar to ulcerative colitis in humans, were made vitamin D deficient (D-) or vitamin D sufficient (D+) or were supplemented with 1,25-dihydroxyvitamin D(3) (1,25D3). 1,25-Dihydroxyvitamin D3 supplementation, but not vitamin D supplementation, reduced the early mortality of IL-2 KO mice. However, colitis severity was not different in D-, D+, or 1,25D3 IL-2 KO mice.