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Vitamin D Presented In Vitro Immunomodulatory Property on T Lymphocyte-Related Cytokines in Systemic Lupus Erythematosus

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Abstract

Inflammatory T lymphocyte cytokines contribute to tissue damage in SLE patients. Vitamin D (Vit D) has a well-established immunomodulatory action, but few studies have addressed the effect of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) on peripheral blood mononuclear cells (PBMCs) in SLE patients. The aim of this study was to evaluate the immnunomodulatory effect of 1,25 (OH)2D3 on T lymphocyte-related cytokines. Blood from 27 female SLE patients was collected for PBMC isolation and anti-DNA, complement, and serum 25 (OH)D3 level measurements. PBMCs were stimulated with anti-CD3/anti-CD28 in the presence or absence of dexamethasone or various concentrations of 1,25 (OH)2D3 for 48 h. We assessed IL-17A, IL-22, IL-21, IL-9, IFN-γ, IL-4, IL-10, IL-2, IL-6, and TNF by cytometric bead assay (CBA) and enzyme immune assay (ELISA) on culture supernatant. The mean age of patients was 36.2 (± 10.5 years) and the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 4 (0–6). The addition of 1,25 (OH)2D3 in PBMC culture reduced IL-17 A, IL-22, IL-9, and IFN-γ levels at 100 nM (p ≤ 0.0001). Furthermore, the addition of 1,25 (OH)2D3 at all concentrations increased IL-4 (p ≤ 0.0006), and 0.1 and 1 nM increased IL-10 (p ≤ 0.0004) and 0.1 nM increased IL-2 levels (p ≤ 0.0001). There was no difference regarding IL-21 and TNF levels. The addition of 1,25 (OH)2D3 in PBMC culture presented an inhibitory effect on proinflammatory cytokines and increased immunoregulatory cytokines in SLE patients, suggesting the beneficial effect of this vitamin.

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Availability of Data and Materials

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

The authors would like to acknowledge all participants.

Funding

This study had partial financial support by the Research Foundation of the Brazilian Rheumatology Society and a research fellowship (E.I. Sato) from the National Council for Scientific and Technological Development (CNPq) of the Brazilian Ministery of Science, Technology and Innovation (MCTI).

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Authors and Affiliations

  1. Rheumatology Division, Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil

    Henrique Ataíde Mariz, Rafaela Gonçalves & Angela Luzia Branco Pinto Duarte

  2. Rheumatology Division, School of Medicine, Federal University of São Paulo, São Paulo, Brazil

    Henrique Ataíde Mariz & Emília Inoue Sato

  3. Laboratory of Immunomodulation and New Therapeutic Approaches (LINAT), Research Center On Therapeutic Innovation Suely Galdino (NUPIT-SG), Federal University of Pernambuco, Recife, Brazil

    Pablo Ramon Gualberto Cardoso, Moacyr Jesus Barreto de Melo Rego, Ivan da Rocha Pitta & Maíra Galdino da Rocha Pitta

  4. Cidade Universitária, CEP 50670-420, Recife, PE, Brazil

    Rafaela Gonçalves

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  1. Henrique Ataíde Mariz
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Contributions

HM, ES, RG, and AD: study concept and design. HM and PC: data collection. HM, MR, IP, and MP: statistical analysis and data interpretation. Further data interpretation and manuscript revision were performed by all the authors. All authors gave final approval of the version to be published. HM prepared the first version of the manuscript.

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Correspondence to Rafaela Gonçalves.

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Mariz, H.A., Sato, E.I., Cardoso, P.R.G. et al. Vitamin D Presented In Vitro Immunomodulatory Property on T Lymphocyte-Related Cytokines in Systemic Lupus Erythematosus. Inflammation 46, 730–738 (2023). https://doi.org/10.1007/s10753-022-01768-0

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