The modulatory effect of high salt on immune cells and related diseases

Abstract

Background: The adverse effect of excessive salt intake has been recognized in decades. Researchers have mainly focused on the association between salt intake and hypertension. However, studies in recent years have proposed the existence of extra-renal sodium storage and provided insight into the immunomodulatory function of sodium.Objectives: In this review, we discuss the modulatory effects of high salt on various innate and adaptive immune cells and immune-regulated diseases. Methods: We identified papers through electronic searches of PubMed database from inception to March 2022. Results: An increasing body of evidence has demonstrated that high salt can modulate the differentiation, activation and function of multiple immune cells. Furthermore, a high-salt diet can increase tissue sodium concentrations and influence the immune responses in microenvironments, thereby affecting the development of immune-regulated diseases, including hypertension, multiple sclerosis, cancer and infections. These findings provide a novel mechanism for the pathology of certain diseases and indicate that salt might serve as a target or potential therapeutic agent in different disease contexts. Conclusion: High salt has a profound impact on the differentiation, activation and function of multiple immune cells. Additionally, an HSD can modulate the development of various immune-regulated diseases. | INTRODUCTIONSalt (NaCl), common in our daily life, can be found naturally in various foods and is used in food manufacturing, the chemical industry, clinical therapy and so forth. For instance, salty condiments contain plenty of NaCl, whereas saline is the most frequently administered intravenous fluid. 1 Although salt is necessary for the human body, excessive salt intake can be detrimental and increase the risk of diseases such as hypertension, heart failure and renal disease. 2 In addition, the immunomodulatory function of salt has been reported. Early studies found that high salt increased the cytokine production in peripheral blood mononuclear cells (PBMCs). 3,4 In the past decades, growing evidence has indicated that high salt can influence various immune cells. Moreover, a high-salt diet (HSD) has a pronounced effect on immuneregulated diseases, and salt is potentially applied in immune therapy. This review will summarize some of the recent advances in the

Somatic growth outcomes in response to an individualized neonatal sodium supplementation protocol

“…Although this difference was not signi cant, it is consistent with ndings of Isemann et al, who demonstrated Na supplementation of 4 mEq/kg/d during day of life 7-35 signi cantly decreased incidence of late onset sepsis and necrotizing enterocolitis [12]. There are emerging data regarding the impact of Na in the regulation of immune function and the in ammatory response, but whether total body Na status impacts preterm infant infection risk requires further investigation [32,33].…”

Multiple Sclerosis and Sodium Toxicity: Controversy and Future Directions for Low-Salt Interventions

“…Shaharabani et al noted that myelin phase transition increases with sodium concentrations > 150 millimoles per liter (mmol/L), which is within the range found in vivo [40]. For example, normal serum sodium levels in rodents and humans are approximately 140 mmol/L, but higher sodium concentrations in lymphoid and interstitial tissue range from 160 to 250 mmol/L sodium [48]. Of relevance, serum sodium concentrations are sensitive to fluid overload in hypervolemia, and clinical hyponatremia should be classified as hypervolemic, hypovolemic, or euvolemic [49].…”

A review of the world's salt reduction policies and strategies – preparing for the upcoming year 2025

“…Animal studies have explored various mechanisms of hypertension by combining high salt intake with the intestinal immune response. 23–25 These studies underscore the gut microbiome as a potential therapeutic target for mitigating salt-sensitive diseases. An article published in 2017 first proposed that a high-salt diet affects the gut flora of mice, specifically reducing the abundance of Lactobacillus .…”