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.
Highlights
Since no data are available on the biological effects of excess sodium in patients with autoimmune diseases, the aim of the present study was to investigate whether the frequency and function of T helper 17 (Th17) and Treg cells are affected by a restriction of dietary sodium intake in Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients observed over a five-week period
Demographic parameters were balanced between the 2 groups with the exception of age, which was significantly higher in patients with RA with respect to those with SLE (p = 0.0008)
We investigated the change in the frequencies of Th17 and Treg cells in the peripheral blood of patients with RA and SLE following a dietary regimen characterized by the modulation of sodium intake
Summary
The role of dietary factors has gained interest due to the results of 2 independent studies, in which a modulation in T cells immune response was observed after a few weeks in murine models of autoimmune diseases following an excess salt intake [3,4]. Both studies demonstrated that high concentrations of sodium chloride promote the differentiation of T helper (Th) lymphocytes toward the Th17 phenotype, known to be highly pro-inflammatory [5], and the Th17-modulating effects of sodium chloride were found to be critical for the development of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS) [3]. A clear association between dietary sodium intake and disease activity could not be claimed because the cohort size was relatively small, the serum sodium levels remained rather constant under different dietary conditions, and the exclusion of confounders was not possible [7]
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