Background/Purpose:  Given the effects of magnesium supplementation in suppressing components of the innate immunity in short-term studies, we examined the effect of dietary magnesium modifications in arthritis severity, a chronic model of autoimmune disease.

Methods: DBA1/J mice were placed on one of two short-term diets before (22-day) the induction of collagen-induced arthritis (CIA) or after disease onset (9-days): low-magnesium diet or normal diet. The diets were then discontinued and converted into a normal diet. CIA activity and arthritis severity was scored for 50 days. Spleens were used for qPCR and FACS, and synovial tissues and cells lines for qPCR.

Results:  Mice on the low magnesium diets were significantly protected and had a >70% lower mean arthritis severity scores in the preventive arm. The group that started the low magnesium diet after the onset of disease also achieved a 50% reduction on their mean severity. The disease protective or ameliorating effects of the low magnesium diet persisted beyond the duration of the diet suggesting a permanent effect on a critical pathogenic pathway. The low magnesium diet mice preserved a normal joint histology without erosive changes. Mice on the low-magnesium diet had significantly reduced synovial tissue expression of IL-6, IL-17, CXCL10, RORA and RORC (genes required or implicated in the development of Th17 T cells), as well as reduced levels of MMP-2 and MMP-3, which are two key mediators of joint damage. Low magnesium concentrations also reduced synovial fibroblast expression of TNFa and IL-6. Spleens from low magnesium diet mice had reduced levels of Th17 T cells and increased numbers of FoxP3+ Treg cells and increased number of IL-10+ CD4+ T cells. In vitro studies demonstrated that low magnesium concentrations (0.1mM and 0.4mM) did not directly affect the differentiation of mouse naïve CD4+ T cells into Th17 T cells, nor affected the amount of IL-17 produced by these cells, suggesting an indirect effect mediated by another cell type.

Conclusion:  This study revealed a novel role for magnesium in the regulation of autoimmune arthritis and opens new possibilities for the treatment of autoimmune diseases such as RA and psoriatic arthritis with short courses of dietary or drug-induced modulations of magnesium levels. We also describe a new effect of low magnesium in suppressing Th17-related genes and MMPs.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/magnesium-is-a-new-mediator-arthritis-severity-and-joint-damage/