Bosch, J. van den (Jacqueline) (2014) The effects of dietary salt intake on the distribution of circulating T-helper cell subsets in humans. thesis, Medicine.
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Abstract
Background: Excessive dietary salt intake (sodium chloride, NaCl) is a main factor in the pathogenesis of cardiovascular and renal damage, which is attributed to an increase in blood pressure in response to sodium. Yet dietary sodium appears to be protective by blood pressure independent mechanisms as well. Data obtained from in vitro and animal studies indicate an effect of sodium on the differentiation and distribution of CD4+ T-cells, also known as T-helper (Th) cells. Th differentiation appears to skew towards the inflammatory Th17 subset in high salt conditions. These Th17 cells play a significant role in inflammation and autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and psoriasis. This study will investigate the effect of a sodium diet on the differentiation of Th cells for the first time in healthy men. Hypothesis: Increased sodium intake diet causes a skewing of Th differentiation towards Th17 cells. Study population: The study population consisted out of 15 healthy men selected from an ongoing randomized cross-over study, comparing low (50 mmol/day) and high (200 mmol /day) sodium intake. The order of these weeks was randomized. In order to investigate dosage effect, three subjects followed an extra sodium diet around 100 mmol/day indicated as medium salt intake. Study design: The study was designed as an experimental clinical study using peripheral blood samples of 15 men from the randomized cross-over study. Heparinized peripheral blood was collected after one week of low sodium diet and one week of high sodium diet. The frequencies of CD4+ T-cell subsets (Th1/Th2/Th17/ TFH) were measured in each sample by multi-color flow cytometry, upon in vitro stimulation with PMA en Ca-Ionophore. Furthermore, blood of 3 healthy blood donors was differentiated in vitro under increasing salt conditions. Results: TNFαlowIl-17+CD4+ T-cells significantly decreased during high sodium diet compared to low sodium diet (p=0.0148). The decrease appeared to be already present at medium salt intake. The decrease in vivo was not associated with clinical parameters. Results of in vitro salt alterations showed an increase of this specific cell subset. Conclusion: Naive Th cells appear to differentiate to a TNFαlowIl-17+ producing Th cells during increased salt conditions. We speculate that these cells migrate to other tissue. These results support the hypotheses that salt intake influences Th differentiation, yet it needs to be confirmed in future studies whether high salt intake leads to towards pathogenic Th17 cells. Longer follow up studies of patients with Th17 mediated autoimmune disease could be of interest.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Abdulahad, dr. W. and Heeringa, prof. P. and Navis, prof. G. and rheumatology and clinical immunology, pathology and medical |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:44 |
| Last Modified: | 25 Jun 2020 10:44 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/533 |
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