Vitamin D3 administration to MS patients leads to increased serum levels of latency activated peptide (LAP) of TGF-beta

Background: Deficiency of vitamin D is an environmental risk factor for MS. Vitamin D has immunomodulatory effects, including promotion of T-cell differentiation into T-regulatory cells, which produces regulatory cytokines including TGF-beta. Increasing serum vitamin D levels have been associated with decreased disease activity in MS patients, but there are only few studies concerning the immunological effects of vitamin D supplementation in MS. In this study we investigated the effect of weekly supplementation of vitamin D3 or placebo on serum levels of multiple cytokines in patients with relapsing remitting MS. Methods: The study was conducted on the patient cohort of the Finnish Vitamin D study. All patients were using IFN-beta-1b and were randomized to add-on treatment with either cholecalciferol 20,000 IU/week or placebo. Concentrations of LAP (TGF-beta), INF-gamma, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1 beta and TNF-alpha were determined at screening and at 12 months using commercial fluorescent bead immunoassay kits. Results: LAP (TGF-beta) levels increased significantly in the vitamin D treated group from a mean of 47 (SE 11) pg/ml to 55 (SE 14) pg/ml in 12 months (p-value = 0.0249). Placebo treatment had no significant effect on LAP levels. The levels of the other cytokines did not change significantly in either group. Conclusions: We showed increased serum latency activated peptide (LAP) of TGF-beta levels in MS patients treated with vitamin D3. The immune regulatory effects of TGF-beta may play a role in the improved MRI outcomes that we observed earlier in the vitamin D treated group of patients. (C) 2015 Elsevier B.V. All rights reserved.