1,25 dihydroxyvitamin D3 limits monocyte maturation in lupus sera

In this study we examined whether treatment with 1,25-dihydroxyvitaminD(3) (1,25(OH)(2)D-3) affects human APC maturation in vitro under multiple cytokine milieus. Human monocytes were elutriated from whole blood, incubated with human sera in the presence or absence of 1,25(OH)(2)D-3, and stimulated with IFN alpha, GM-CSF/IL-4, or were cultured without stimulatory cytokines. Incubation of control monocytes with 1,25(OH)(2)D-3 limited expression of cell surface makers of maturation whether monocytes were stimulated in IFN alpha, GM-CSF/IL-4, or in serum alone. The ability of 1,25(OH)(2)D-3 to affect human monocyte phenotype was assessed by incubating cells with sera from 15 patients with SLE and from 5 healthy volunteers. Addition of 1,25(OH)(2)D-3 resulted in significant reductions in the expression of MHC Class II, CD40, and CD86 and increases in expression of CD14 in both types of sera. Overall, 1,25(OH)(2)D-3 limited human APC activation via IFN alpha-induced and independent mechanisms. 1,25(OH)(2)D-3 inhibited APC activation by systemic lupus erythematosus (SLE) sera, suggesting that it may be possible for 1,25(OH)(2)D-3 to reduce the immunostimulatory effects of the SLE milieu by interfering with the soluble cytokine mediators in the sera of SLE patients. Lupus (2011) 20, 749-753.