Salt Behind the Scenes of Systemic Lupus Erythematosus and Rheumatoid Arthritis

Sodium is vital for human health. High salt intake is a global health problem and is associated with cardiovascular morbidity and mortality. Recent evidence suggests that both innate and adaptive immune systems are affected by sodium. In general, excess salt intake drives immune cells toward a pro-inflammatory phenotype. The incidence of autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), is steadily increasing. As excess salt induces a pro-inflammatory state, increased salt intake may have impacts on autoimmune diseases. The relationship between salt intake and autoimmune diseases is most widely studied in patients with SLE or RA. This review aimed to summarize the relationship between salt intake and SLE and RA.

Most, but not all, of these studies showed that high salt intake might promote SLE by M1 macrophage shift, increase in Th17/Treg cell ratio, activation of dendritic and follicular helper T cells, and increased secretion of pro-inflammatory cytokines. In RA, apart from driving immune cells toward a pro-inflammatory state, high salt intake also influences cellular signaling pathways, including receptor activator of nuclear factor κB ligand (RANKL), Rho GTPases, and MAPK (mitogen-activated protein kinase). There is now sufficient evidence that excess salt intake may be related to the development and progression of SLE and RA, although there are still knowledge gaps. More studies are warranted to further highlight the relationship between excess salt intake, SLE, and RA. Salt intake may affect cell types and pro-inflammatory cytokines and signaling pathways associated with the development and progression of systemic lupus erythematosus and rheumatoid arthritis. Bcl-6 B-cell lymphoma, 6 Erk extracellular signal-regulated kinases, IFN-γ interferon-gamma, JNK c-Jun N-terminal kinase, IL-4 interleukin 4, IL-6 interleukin 6, MAPK mitogen-activated protein kinase, STAT signal transducer and activator of transcription, Tnf-α tumor necrosis factor, Treg T regulatory cell.