gms | German Medical Science

Introduction: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease going along with severe organ damage, such as nephritis, hematologic or neurological complications. SLE is characterized by a loss of self-tolerance, a broad immune dysregulation and production of autoantibodies against nuclear self-antigens. Although the exact mechanisms are still unresolved, it becomes increasingly clear that SLE pathogenesis results from a complex interplay between genetic and environmental factors. In SLE, disturbed macrophage function, specifically a defective phagocytosis, has been described and may be central to the break of tolerance and disease pathology. Both vitamin A and vitamin D have pleiotropic and possibly anti-inflammatory effects on macrophages and monocytes.

Methods: Aim of this study was to examine the effects of vitamin D and A on macrophage differentiation, polarization and phagocytic capacity and their impact on lupus pathogenesis. The first question was addressed by in vitro and in vivo approaches on the basis of human and murine monocytes and macrophages. Effects on lupus pathology were tested in lupus-prone NZB/WF1 mice. These were continuously fed a diet containing high, normal and low vitamin D (cholecalciferol) concentrations. One group of mice also received the active vitamin D metabolite, 1α,25-dihydroxyvitamin D.

Results: Our preliminary in vitro data indicate that both Vitamin D and A can influence phagocytosis, although effects vary depending on macrophage differentiation. Our data further suggest that a vitamin D-deficiency slightly accelerates lupus pathology as determined by overall survival, proteinuria and anti-dsDNA production. However, we did not observe a clear association between disease progression and a reduced phagocytic macrophage function in Vitamin D deficient animals. Thus, we are currently examining further immunologic dysregulations underlying the changed disease pathology.

Conclusion: Altogether, our data suggest immune-modulatory effects of vitamin D and vitamin A with potential therapeutic potential.

Disclosures: keine