Too Much Salt may Lower Immunity, Finds Study

Serum sodium transiently increases postprandially, but can also accumulate at sites of inflammation affecting differentiation and function of innate and adaptive immune cells. Several studies suggest the risk of high sodium intake. However, the effect of HS at the cellular level remains understudied. Therefore, Dr Sabrina Geisberger and her team conducted a study to investigate how changes in extracellular sodium, mimicking alterations in the circulation and tissues, affect the early metabolic, transcriptional and functional adaption of human and murine mononuclear phagocytes (MNP).

In an in-vitro study, researchers used seahorse technology, pulsed stable isotope-resolved metabolomics and enzyme activity assays to characterize the central carbon metabolism and mitochondrial function of human and murine MNP under HS invivo.

They used HS as well as pharmacologic uncoupling of the electron transport chain (ETC) under normal salt (NS) to analyze mitochondrial function on immune cell activation and function.

They further conducted two independent clinical studies (invivo) to analyze the impact of an HS diet over two weeks and a short-term salt challenge by a single meal on the mitochondrial function of human monocytes.

Key findings of the study were:

• Upon in-vitro study, the researchers observed changes within 3 hours.
• They observed that extracellular sodium was taken up into the intracellular compartment followed by the inhibition of mitochondrial respiration in murine and human macrophages (MΦ).
• They found that HS reduced mitochondrial membrane potential, ETC complex II activity, oxygen consumption, and ATP production independently of the polarization status of MΦ.
• The lack of energy causes the monocytes to mature differently. "The phagocytes, whose task is to identify and eliminate pathogens in the body, were able to fight off infections more effectively. But this could also promote inflammation, which might increase cardiovascular risk," explains Müller.
• Upon in-vivo study, they noted that a rise in plasma sodium concentration within the physiological range reversibly reduces mitochondrial function in human monocytes.
• Upon 14-day and single meal HS challenge, they noted that healthy volunteers displayed a plasma sodium increase of ̃x = 2mM and ̃x = 2.3mM, respectively, that correlated with decreased monocytic mitochondrial oxygen consumption.

The authors concluded, "Our data identify the disturbance of mitochondrial respiration as the initial step by which high salt mechanistically influences immune cell function. While these functional changes might help to resolve bacterial infections, a shift towards pro-inflammation could accelerate inflammatory CVD."

For further information:

https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.052788