Sodium-restricted diet has no effect on plasma IL-17 but reduces plasma IL-1β, IL-6, and IL-22 in patients with treatment-resistant hypertension

Hypertension is a major risk factor for cardiovascular disease and is increasingly recognized as being associated with chronic low-grade inflammation. Preclinical models have identified a potential causal role for interleukin-17 (IL-17) in the pathogenesis of salt-sensitive hypertension; however, evidence from human interventional studies remains sparse. We therefore performed a post hoc analysis of circulating IL-17 family cytokines and related inflammatory mediators in plasma samples obtained from patients with treatment-resistant hypertension before and after a controlled dietary sodium-restriction intervention. Ten cytokines were measured in paired plasma samples from 15 patients with treatment-resistant hypertension using Mesoscale multiplex assays, obtained before and after a 14-day sodium-restricted diet as part of a previously published interventional study and correlated with blood pressure and urinary sodium excretion. Sodium restriction decreased 24-hour systolic blood pressure by 10 ± 8 mmHg and 24-hour urinary sodium excretion by 96 mmol/day. Plasma levels of IL-17 A, IL-17E/IL-25, and IL-17 F did not change significantly following sodium restriction. IFN-γ increased in the primary analysis but was no longer statistically significant after excluding one assumed outlier, whereas IL-1β, IL-6, and IL-22 decreased significantly. These changes were not statistically associated with changes in blood pressure or urinary sodium excretion. Short-term dietary sodium restriction was associated with reductions in several circulating pro-inflammatory cytokines, including IL-1β, IL-6 and IL-22, whereas circulating IL-17 cytokines remained unchanged. The observed cytokine changes were not significantly correlated with changes in blood pressure, and further studies are needed to clarify their clinical and mechanistic relevance. The original study was prospectively registered at ClinicalTrials.gov (NCT06022133) in January 2018.