Dietary calcium is a major factor in 1,25-dihydroxycholecalciferol suppression of experimental autoimmune encephalomyelitis in mice

The active form of vitamin D (1,25-dihydroxycholecalciferol) is a potent im mune system regulator. Treating mice with 1,25-dihydroxycholecalciferol and feeding them diets high in calcium can completely suppress the induction o f experimental autoimmune diseases such as experimental autoimmune encephal omyelitis (EAE). Experiments described here were carried out on mice in whi ch development of EAE was induced. Mice were fed diets containing various a mounts of calcium and 1,25-dihydroxychole-calciferol. Variables measured we re as follows: 1) incidence and severity of EAE; 2) serum calcium concentra tions; 3) body weight; 4) total number of cells in the lymph nodes; and 5) interleukin-4 (IL-4) and transforming growth factor-beta 1 (TGF-beta 1) mRN A levels. When calcium was removed from the diet, the incidence of EAE was reduced 20% in both males and females. Further, the lower the dietary level of calcium, the higher was the dose of 1,25-dihydroxycholecalciferol requi red to prevent the symptoms. Thus, 1,25-dihydroxycholecalciferol was found most effective in mice fed a diet adequate or high in calcium. 1,25-Dihydro xychorecalciferol treatment of mice fed high dietary calcium resulted in a decreased number of lymphocytes in the lymph nodes and increased IL-4 and T GF-beta 1 mRNA levels. When calcium was omitted from the diet, 1,25-dihydro xycholecalciferol supplementation increased TGF-beta 1 mRNA. Increased IL-4 mRNA and decreased lymphocytes in the lymph nodes in response to 1,25-dihy droxycholecalciferol occurred only when dietary calcium was adequate or hig h. Our results suggest that dietary calcium and 1,25-dihydroxycholecalcifer ol are both involved in the prevention of symptomatic EAE.