AB0035 Vitamin d down-regulates pro-inflammatory cytokine response in rheumatoid arthritis peripheral macrophages
Authors: A. Corrado, A. Neve, F. P. Cantatore
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent data support the hypothesis that Vitamin D is able to modulate several extra-skeletal biological functions, including immune response; it has been found that Vitamin D exerts an immune-modulatory effect on various cells of immune system. Low Vitamin D serum levels have been recently related to the pathogenesis of different autoimmune disease; particularly, in Rheumatoid Arthritis (RA), Vitamin D deficiency has been found to be associated with increased susceptibility to development of disease and appears to be related to disease activity. Experimental studies showed that Vitamin D treatment can modulate the inflammatory response in RA synovial cells and in animal models of RA. <h3>Objectives</h3> The aim of this study is to evaluate the <i>in vitro</i> effect of Vitamin D on peripheral macrophages derived from RA patients, which represent one of a major source of inflammatory mediators in this disease. <h3>Methods</h3> Macrophages derived from peripheral blood cells were isolated from 15 RA untreated patients (5 men, 10 women; age 55,2±7,32 years, range: 42-65), and 11 healthy subjects (2 men, 9 women, age 48,3±6,2 years, range: 41-61). All patients fulfilled the 2010 revised American College of Rheumatology criteria for RA, with a disease duration &lt; 1 year, and presented a moderate disease activity (3.2&lt;DAS28&lt;5,1). RA and control macrophages were treated with increasing concentrations (10<sup>-10</sup> to 10<sup>-7</sup> M) of 1,25(OH)<sub>2</sub>D<sub>3</sub> for 24h. In each experimental conditions, TNF-α, IL-1 α, IL-1 ß, IL-6 and RANKL production was evaluated by ELISA; the expression of trans-membrane TNF-α was evaluated by immunocytochemistry analysis. Nitric oxide (NO) release was determined by the colorimetric Griess method. <h3>Results</h3> As expected, inflammatory cytokine production was higher in RA macrophages compared to the control ones. In RA macrophages, soluble TNF-α production was significantly reduced by 1,25(OH)<sub>2</sub>D<sub>3</sub> treatment at any used concentrations, in a dose-dependent manner, whereas in control cells only higher concentrations of 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibited TNF-α production. Also trans-membrane TNF-a expression was down-regulated by 1,25(OH)<sub>2</sub>D<sub>3</sub> exposure, in a dose dependent manner, both in normal than in RA macrophages. IL-1 and IL-6 production was significantly reduced only by higher 1,25(OH)<sub>2</sub>D<sub>3</sub> concentrations both in RA and control cells. RANKL and NO were decreased in RA macrophages by any 1,25(OH)<sub>2</sub>D<sub>3</sub> tested concentrations, in a dose-dependent manner, whereas in normal macrophages RANKL and NO reduction was observed only with higher 1,25(OH)<sub>2</sub>D<sub>3</sub> concentrations. <h3>Conclusions</h3> The presented data show that Vitamin D is able to reduce pro-inflammatory and pro-osteoclastogenic cytokines levels and NO production in RA peripheral macrophages, suggesting that a Vitamin D supplementation could reduce disease severity and protect bone from erosive damage. Additional investigations are needed to evaluate the use of Vitamin D as adjuvant therapy in RA in clinical practice. <h3>References</h3> Kostoglou-Athanassiou I, Athanassiou P, Lyraki A et al. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2012 Dec;3(6):181-7 Villaggio B, Soldano S, Cutolo M. 1,25-dihydroxyvitamin D3 downregulates aromatase expression and inflammatory cytokines in human macrophages. Clin Exp Rheumatol. 2012 Nov-Dec;30(6):934-8 <h3>Disclosure of Interest</h3> None Declared