Discussion
autoimmune disease, hypertensive
AUTOIMMUNE DISORDERS, AUTOIMMUNE DISEASE
The results from our clinical study show that the diet (fish and vegetable enriched Healthy Nordic Diet) or reduced salt intake does not change the levels of circulating cytokines in humans. We find the placebo‐controlled cross‐over study design, objective measurement of sodium excretion and relatively long duration (8+8 wk interventions) as strengths of our study. The provocative results on the salt‐induced Th2 and Th17 expansion, and their association with aggravated autoimmune reactivity in mice, thus seem not to be directly translatable into humans under physiologically relevant in vivo settings.The reasons for the discrepant results between our study and those using mouse models may include genuine species‐specific differences in electrolyte metabolism and immune cell activation. Moreover, in the in vivo mouse experiments the animals have been suddenly exposed to chow, which contains 4–5% salt [A few studies have reported salt‐induced changes in cytokine secretion in humans under in vivo settings. In a spaceflight stimulation study (an enclosed habitat) six healthy males were subjected to fixed salt intake (daily doses of 12 g, 9 g, and 6 g salt; about 50 days under each condition) in a context of a very carefully controlled diet. Analyses of plasma TNFα, IL‐6, IL‐10 and IL‐17 did not reveal statistically different changes during the different salt ingestion phases [Mediterranean diet is consistently found to lower the systemic levels of pro‐inflammatory biomarkers [Our study has several limitations. It includes a relatively small and heterogeneous group of mildly hypertensive individuals. The power calculations were done for the primary end point (blood pressure) and therefore higher number of participants would have increased the power of several cytokine analyses, although the cross‐over setup (each individual serving as her/his own control) is a clear strength in our study. Moreover, we cannot exclude the possibility that longer (or shorter) alterations in salt or diet would have altered cytokine levels. However, in other studies other types of dietary interventions have resulted in detectable alterations in cytokine levels in less than 8 weeks (e.g., [In conclusion, our data suggest that increased salt intake at the levels seen in everyday life do not affect systemic cytokine levels in humans. Therefore, salt induced changes in cytokines are unlikely to induce the differentiation of pathogenic Th2 and Th17 responses in humans. These observations have important implications in immunology and medicine, since they do not support the literature proposing that increased salt intake might precipitate the emergence of autoimmune disease or that restricting salt intake would be a therapeutic option for treating autoimmune disorders.