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Ann Rheum Dis 72:473-475 doi:10.1136/annrheumdis-2012-202538
  • Editorial

Further emergent evidence for the vitamin D endocrine system involvement in autoimmune rheumatic disease risk and prognosis

  1. Maurizio Cutolo
  1. Research Laboratory and Academic Clinical Unit of Rheumatology, Division of Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy
  1. Correspondence to Professor Maurizio Cutolo, Research Laboratory and Academic Clinical Unit of Rheumatology, Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto, XV, 6, Genova, Italy;mcutolo{at}unige.it
  • Received 27 October 2012
  • Revised 30 December 2012
  • Accepted 1 January 2013

Vitamin D: a true endogenous immunomodulator

Recently, vitamin D has received increased worldwide attention for its involvement in reducing risk for several chronic diseases including many cancers, infectious diseases, type 1 diabetes and notably autoimmune rheumatic diseases.1

The final active metabolite of vitamin D (1,25(OH)D3) is considered a steroid hormone for its origin from cholesterol (D-hormone), and like glucocorticoids exerts immunomodulatory activities (figure 1).2 ,3

Figure 1

Newly identified target genes for calcitriol (D hormone) reveal multiple molecular pathways of anti-inflammatory actions for 1,25(OH)D3 in several cell types. These include: inhibition of prostaglandin (PG) synthesis and biological actions; inhibition of p38 stress kinase activation and production of proinflammatory cytokines such as IL-6 (via induction of MAP kinase phosphatase 5 (MKP5 expression); inhibition of nuclear factor κB (NF-κB) signalling which results in the attenuation of the synthesis of proinflammatory cytokines such as interleukin-8 (IL-8) (via up-regulation of the expression of insulin-like growth factor binding protein-3 (IGFBP-3); inhibition of angiogenesis due to suppressive effects on the expression of proangiogenic factors such as hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor; increase in the expression of E-cadherin, leading to the inhibition of invasion and metastasis. Solid lines indicate direct actions of calcitriol, and dotted lines indicate downstream effects of calcitriol.

Pathophysiological investigations confirm that severe hypovitaminosis D, in genetically predisposed subjects, can impair self tolerance and immune responses by compromising the regulation of dendritic cells, regulatory T-lymphocytes (Tregs), Th1 cells and B cell function.3

Cross-sectional studies have shown that deficient serum levels of vitamin D (25(OH)D) (<20 ng/ml) are present in a significant percentage, not only in patients with autoimmune diseases such as multiple sclerosis (MS), type 1 diabetes, systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), but also in healthy subjects.4 ,5 In addition, the presence of severe 25(OH)D deficiency (<10 ng/ml) …