1,25 dihydroxyvitamin D ₃ limits monocyte maturation in lupus sera

Abstract

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 IFNα, 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 IFNα, 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 IFNα-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.