High-dose vitamin D in Addison's disease regulates T-cells and monocytes: A pilot trial.

OBJECTIVES: On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD).

METHODS: This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D3 ) levels and immune cells including T helper cells (Th; CD3+ CD4+ ), late-activated Th cells (CD3+ CD4+ HLA-DR+ ), regulatory T cells (CD3+ CD4+ CD25bright CD127dim/neg ), cytotoxic T cells (Tc; CD3+ CD8+ ), late-activated Tc cells (CD3+ CD8+ HLA-DR+ ), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers.

RESULTS: Ten of 13 patients (77%) were VD deficient. Median 25(OH)D3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed.

CONCLUSIONS: Three months of treatment with cholecalciferol achieved sufficient 25(OH)D3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD.