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Vitamin D Deficiency and Rheumatoid Arthritis

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Abstract

Vitamin D (VitD) is a hormone primarily synthesized in human skin under the stimulation of ultraviolet radiation. Beyond its endocrine role in bone metabolism, VitD is endowed with remarkable immunomodulatory properties. The effects of VitD on the immune system include the enhancement of microbicidal ability of monocytes/macrophages and the down-modulation of inflammatory cytokines produced by T lymphocytes. VitD deficiency is involved in many health problems, including immune-mediated diseases such as autoimmune disorders. Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease that compromises the joints, causing cartilage destruction and bone erosion. RA treatment usually consists of combined therapies that generally suppress the entire immune response leading to increased susceptibility to infections. This review describes the main effects of VitD on innate and adaptive immune system and also VitD status in inflammatory rheumatic diseases such as RA. Despite some controversies, the majority of reports reinforce the idea that lower VitD levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. Therefore, supplementation with VitD to achieve normal serum levels is worthwhile as an aforethought. Original data concerning the potential applicability of 1,25-dihydroxyvitamin D3 (VitD3), the active form of vitamin D, as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3 associated with proteoglycan (PG), which is a specific cartilage antigen, was tested in the course of experimental arthritis. This association significantly lowered clinical scores and local histopathological alterations. Even though local analysis of T cell subsets and cytokine production did not reveal any difference between the experimental groups, VitD3+PG association significantly reduced cytokine production by spleen cells. These results suggest that VitD3 played a role as a tolerogenic adjuvant by down-modulating the course of experimental RA. Considering this tolerogenic effect of VitD3+PG association, further investigations will reveal its plausible use in human RA.

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Acknowledgments

The authors are thankful to São Paulo State Foundation (FAPESP) for the financial support. Special thanks are given to Prof. Yehuda Shoenfeld, Mrs. Anna Varsanyi, and the Federico Fellows from the Zabludowicz Center for Autoimmune Diseases, Israel, for the scientific contribution.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil

    Larissa Lumi Watanabe Ishikawa, Priscila Maria Colavite, Thais Fernanda de Campos Fraga-Silva, Luiza Ayumi Nishiyama Mimura, Thais Graziela Donegá França, Sofia Fernanda Gonçalves Zorzella-Pezavento, Fernanda Chiuso-Minicucci & Alexandrina Sartori

  2. Department of Pathology, Botucatu Medical School, Botucatu, São Paulo, Brazil

    Larissa Doddi Marcolino

  3. Flow Cytometry Laboratory, Amaral Carvalho Foundation, Jaú, São Paulo, Brazil

    Marcimara Penitenti & Maura Rosane Valerio Ikoma

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  1. Larissa Lumi Watanabe Ishikawa
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  2. Priscila Maria Colavite
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Correspondence to Larissa Lumi Watanabe Ishikawa.

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The authors declare that they have no conflict of interest.

Funding

This study was funded by São Paulo State Foundation (grant no. 2011/17325-4 and grant no. 2010/20470-3).

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Ishikawa, L.L.W., Colavite, P.M., Fraga-Silva, T.F.d.C. et al. Vitamin D Deficiency and Rheumatoid Arthritis. Clinic Rev Allerg Immunol 52, 373–388 (2017). https://doi.org/10.1007/s12016-016-8577-0

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