The role of dietary sodium intake on the modulation of T helper 17 cells and regulatory T cells in patients with rheumatoid arthritis and systemic lupus erythematosus

Abstract

We aimed at investigating whether the frequency and function of T helper 17 (Th17) and regulatory T cells (Treg) are affected by a restriction of dietary sodium intake in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We enrolled RA and SLE patients not receiving drugs known to increase urinary sodium excretion. Patients underwent a dietary regimen starting with a restricted daily sodium intake followed by a normal-sodium daily intake. The timepoints were identified at baseline (T0), after 3 weeks of low-sodium dietary regimen (T3), after 2 weeks of normal-sodium dietary regimen (T5). On these visits, we measured the 24-hour urinary sodium excretion, the frequency and function of Th17 and Treg cells in the peripheral blood, the serum levels of cytokines. Analysis of urinary sodium excretion confirmed adherence to the dietary regimen. In RA patients, a trend toward a reduction in the frequencies of Th17 cells over the low-sodium dietary regimen followed by an increase at T5 was observed, while Treg cells exhibited the opposite trend. SLE patients showed a progressive reduction in the percentage of Th17 cells that reached a significance at T5 compared to T0 (p = 0.01) and an increase in the percentage of Treg cells following the low-sodium dietary regimen at both T1 and T3 compared to T0 (p = 0.04 and p = 0.02, respectively). No significant apoptosis or proliferation modulation was found. In RA patients, we found a reduction at T5 compared to T0 in serum levels of both TGFβ (p = 0.0016) and IL-9 (p = 0.0007); serum IL-9 levels were also reduced in SLE patients at T5 with respect to T0 (p = 0.03). This is the first study investigating the effects of dietary sodium intake on adaptive immunity. Based on the results, we hypothesize that a restricted sodium dietary intake may dampen the inflammatory response in RA and SLE patients.

Western and Healthy Dietary Patterns and Risk of Rheumatoid Arthritis: A Case-Control Study

“…A case-control study showed a correlation between the monounsaturated fatty acids (MUFA) intake and suppression of RA activity (28). Clinical trials have documented decreases in inflammatory responses and disease activities following sodium restriction (29) or ingestion of fish oil ω-3-fatty acids (30). Despite the highlighted studies, associations between the diet and RA risk were not seen in a prospective cohort with a relatively short duration (5.3 years of follow-ups) and limited incident cases (31).…”

“…For example, the high SFA in Western dietary pattern activates toll-like receptor mediated inflammatory pathways through oxidative modifications of low-density lipoproteins (39). Salt, another ingredient of the Western dietary pattern, enhances differentiation of interleukin-17 producing helper T-cells, which are responsible for the development of arthritis (29). Whole grains in the healthy dietary pattern decrease inflammations (40,41), while sweets and refined grains in the Western dietary pattern causes high glycemic loads, leading to persistent hyperglycemia, production of advanced glycation products, insulin resistance and initiation of inflammatory cascade (42)(43)(44).…”

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…Additionally, animal data demonstrate that high salt intake can result in worsening of inflammatory conditions, including models of multiple sclerosis, IBD, and RA . In humans, salt intake can modulate the Th17 polarization of T cells . To our knowledge, there are no trials exclusively evaluating the impact of low‐sodium diets, although EEN and anti‐inflammatory diets used in IBD are low in sodium content.…”

“…152 In humans, salt intake can modulate the Th17 polarization of T cells. 152,153 To our knowledge, there are no trials exclusively evaluating the impact of low-sodium diets, although EEN and anti-inflammatory diets used in IBD 137,138 are low in sodium content.…”

Quantitative Predictive Modelling Approaches to Understanding Rheumatoid Arthritis: A Brief Review

“…Other lifestyle and environmental factors that can increase the risk of RA include alcohol consumption, diet and exposure to occupational and atmospheric agents, such as silica dust and carbon-derived nanoparticles [19,22,40,16,104]. Moreover, some bacterial infections (e.g., Porphyromonas gingivalis [8]) and viral infections (e.g., Epstein-Barr virus [10]) have been associated with RA development [91].…”