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

Abstract

In this study we examined whether treatment with 1,25-dihydroxyvitaminD₃ (1,25(OH)₂D₃) 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)₂D₃, and stimulated with IFNα, GM-CSF/IL-4, or were cultured without stimulatory cytokines. Incubation of control monocytes with 1,25(OH)₂D₃ 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)₂D₃ 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)₂D₃ 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)₂D₃ limited human APC activation via IFNα-induced and independent mechanisms. 1,25(OH)₂D₃ inhibited APC activation by systemic lupus erythematosus (SLE) sera, suggesting that it may be possible for 1,25(OH)₂D₃ to reduce the immunostimulatory effects of the SLE milieu by interfering with the soluble cytokine mediators in the sera of SLE patients.

Keywords

antigen-presenting cells monocytes systemic lupus erythematosus vitamin D

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