Background 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.
Objectives The aim of this study is to evaluate the in vitro effect of Vitamin D on peripheral macrophages derived from RA patients, which represent one of a major source of inflammatory mediators in this disease.
Methods 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 < 1 year, and presented a moderate disease activity (3.2<DAS28<5,1). RA and control macrophages were treated with increasing concentrations (10-10 to 10-7 M) of 1,25(OH)2D3 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.
Results 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)2D3 treatment at any used concentrations, in a dose-dependent manner, whereas in control cells only higher concentrations of 1,25(OH)2D3 inhibited TNF-α production. Also trans-membrane TNF-a expression was down-regulated by 1,25(OH)2D3 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)2D3 concentrations both in RA and control cells. RANKL and NO were decreased in RA macrophages by any 1,25(OH)2D3 tested concentrations, in a dose-dependent manner, whereas in normal macrophages RANKL and NO reduction was observed only with higher 1,25(OH)2D3 concentrations.
Conclusions 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.
References 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
Disclosure of Interest None Declared
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