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Inflammatory cytokines regulate renal sodium transporters: how, where, and why?
Allison E Norlander1, Meena S Madhur2,3
1Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville Tennesee; and.
Insights
Inflammation impacts kidney function and blood pressure regulation. Specific inflammatory cytokines alter sodium transporters, contributing to hypertension, a major global health issue.
Area of Science:
- Nephrology
- Immunology
- Cardiovascular Science
Background:
- Hypertension is a leading preventable cause of premature death globally.
- The kidney is crucial for blood pressure regulation, with renal sodium transport abnormalities linked to elevated blood pressure.
- Recent discoveries highlight the role of inflammatory cytokines in modulating kidney function and blood pressure.
Purpose of the Study:
- To review the role of inflammatory cytokines in modulating renal sodium transporters.
- To discuss the link between cytokine-regulated transporters and hypertension.
- To explore the evolutionary basis for this inflammatory function.
Main Methods:
- Literature review of studies on cytokines, sodium transporters, and hypertension.
- Analysis of mechanisms by which cytokines affect renal epithelial cells.
- Synthesis of evidence linking inflammatory pathways to blood pressure dysregulation.
Main Results:
- Specific inflammatory cytokines have been identified that modulate key sodium transporters along the nephron.
- These modulations lead to altered pressure natriuresis and impaired sodium/water balance.
- Immune cells and renal cells are sources of these hypertension-influencing cytokines.
Conclusions:
- Inflammatory cytokines are significant modulators of renal sodium transport and play a critical role in hypertension.
- Understanding these cytokine-transporter interactions offers potential therapeutic targets for hypertension.
- The evolutionary role of inflammatory cytokines in blood pressure regulation warrants further investigation.
Abstract:
Hypertension is growing in epidemic proportions worldwide and is now the leading preventable cause of premature death. For over a century, we have known that the kidney plays a critical role in blood pressure regulation. Specifically, abnormalities in renal sodium transport appear to be a final common pathway that gives rise to elevated blood pressure regardless of the nature of the initial hypertensive stimulus. However, it is only in the past decade that we have come to realize that inflammatory cytokines secreted by innate and adaptive immune cells, as well as renal epithelial cells, can modulate the expression and activity of sodium transporters all along the nephron, leading to alterations in pressure natriuresis, sodium and water balance, and ultimately hypertension. This mini-review highlights specific cytokines and the transporters that they regulate and discusses why inflammatory cytokines may have evolved to serve this function.
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