Immune regulatory effects of high dose vitamin D-3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFN beta; the SOLARIUM study

Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D-3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study. Thirty Dutch relapsing remitting (RR) MS patients treated with IFN beta-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48 weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytolcine secretion was assessed in the presence or absence of 1,25(OH)(2)D-3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups. The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4(+) Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGF beta, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3. In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS.