Abstract
Objective To determine the effect of vitamin D3 on interferon-β (IFN-β) response and immune regulation in MS mononuclear cells (MNCs).
Methods MNCs from 126 subjects, including therapy-naive patients with different forms of MS, plus patients with MS receiving IFN-β or glatiramer treatment, plus healthy controls were incubated in vitro with IFN-β-1b ± vitamin D3 (calcitriol). Activation of the IFN-β–induced transcription factor, p-Y-STAT1, and antiviral myxovirus A (MxA) protein was measured with flow cytometry and Western blots; serum proteins were measured with a customized 31-protein multiplex assay.
Results Vitamin D enhanced in vitro IFN responses, as measured by induction of p-Y-STAT1 and MxA in MNCs, T cells, and monocytes. Vitamin D augmentation of IFN responses was seen in untreated and in IFN-β-1b–treated MS. The combination of vitamin D plus IFN-β reduced Th1 and Th17 cytokines, and increased Th2 responses, reversing the effect of IFN-β alone. Exacerbations and progression in untreated patients reduced the vitamin D enhancement of IFN responses. Vitamin D had less effect on IFN response in clinically stable glatiramer-treated than in IFN-β–treated patients.
Conclusion Vitamin D enhances IFN-β induction of multiple proteins and also reverses the Th1/Th2 bias in MS seen with IFN-β alone. The combination of vitamin D and IFN-β has potential benefit in ameliorating MS.
Glossary
- BDNF=
- brain-derived neurotrophic factor;
- ConA=
- concanavalin A;
- EAE=
- experimental autoimmune/allergic encephalomyelitis;
- GA=
- glatiramer acetate;
- HC=
- healthy control;
- HGF=
- hepatocyte growth factor;
- IFN-β=
- interferon-β;
- LIF=
- leukemia inhibitory factor;
- MFI=
- median fluorescence intensity;
- MNC=
- mononuclear cell;
- MxA=
- myxovirus A;
- NGF=
- nerve growth factor;
- PMA=
- phorbol myristate acetate;
- PMS=
- progressive MS;
- PPMS=
- primary progressive MS;
- RRMS=
- relapsing/remitting MS;
- RRMS-a=
- active RRMS;
- RRMS-s=
- stable RRMS;
- SPMS=
- secondary progressive MS;
- TPO=
- thymopoietin;
- VDR=
- vitamin D receptor;
- VDSI=
- Vitamin D Stimulation Index
Footnotes
Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.
The Article Processing Charge was funded by the authors.
↵* These authors contributed equally to this work.
- Received April 8, 2019.
- Accepted in final form August 13, 2019.
- Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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