Vitamin D enhances responses to interferon-β in MS

Objective To determine the effect of vitamin D3 on interferon-beta (IFN-beta) 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-beta or glatiramer treatment, plus healthy controls were incubated in vitro with IFN-beta-1b +/- vitamin D3 (calcitriol). Activation of the IFN-beta-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-beta-1b-treated MS. The combination of vitamin D plus IFN-beta reduced Th1 and Th17 cytokines, and increased Th2 responses, reversing the effect of IFN-beta 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-beta-treated patients. Conclusion Vitamin D enhances IFN-beta induction of multiple proteins and also reverses the Th1/Th2 bias in MS seen with IFN-beta alone. The combination of vitamin D and IFN-beta has potential benefit in ameliorating MS.