Renal Effects of Cytokines in Hypertension

Yi Wen; Steven D. Crowley


Curr Opin Nephrol Hypertens. 2018;27(2):70-76. 

In This Article

Abstract and Introduction


Purpose of review: Inflammatory cytokines contribute to the pathogenesis of hypertension through effects on renal blood flow and sodium handling. This review will update recent advances that explore the renal actions of immune cells and cytokines in the pathogenesis of hypertension.

Recent findings: Populations of cells from both the innate and adaptive immune systems contribute to hypertension by modulating functions of the vasculature and epithelial cells in the kidney. Macrophages and T lymphocytes can directly regulate the hypertensive response and consequent target organ damage. Dendritic cells and B lymphocytes can alter blood pressure (BP) indirectly by facilitating T-cell activation. Proinflammatory cytokines, including tumor necrosis factor-α, interleukin 17, interleukin 1, and interferon-γ augment BP and/or renal injury when produced by T helper 1 cells, T helper 17 cells, and macrophages. In contrast, interleukin 10 improves vascular and renal functions in preclinical hypertension studies. The effects of transforming growth factor-β are complex because of its profibrotic and immunosuppressive functions that also depend on the localization and concentration of this pleiotropic cytokine.

Summary: Preclinical studies point to a key role for cytokines in hypertension via their actions in the kidney. Consistent with this notion, anti-inflammatory therapies can attenuate BP elevation in human patients with rheumatologic disease. Conversely, impaired natriuresis may further polarize both T lymphocytes and macrophages toward a proinflammatory state, in a pathogenic, feed-forward loop of immune activation and BP elevation. Understanding the precise renal actions of cytokines in hypertension will be necessary to inhibit cytokine-dependent hypertensive responses while preserving systemic immunity and tumor surveillance.


Hypertension afflicts more than 1 billion people worldwide and is a prominent risk factor for cardiovascular complications.[1] Kidney and cardiovascular dysfunction are causes and also consequences of persistent hypertension, culminating in a high risk of mortality.[2] Despite an armamentarium of pharmacologic therapies that target renal sodium handling, systemic vascular responses, cardiac output, and sympathetic outflow, blood pressure (BP) remains uncontrolled in up to 50% of hypertensive patients.[2,3] Recent studies have revealed that cells of the immune system contribute to the pathogenesis of hypertension via their actions in the kidney, the vasculature, and the brain, such that immunomodulation may represent a novel approach to reduce BP and limit target organ damage in hypertension.[4–6] However, to mitigate the immune system's contribution to hypertension without subjecting patients to unacceptable risks of immunosuppression, the precise mechanisms through which innate and adaptive immunity regulate BP require elucidation. Hematopoietic cells could modulate the functions of cardiovascular control centers, including the kidney by instigating cellular injury or repair, by altering local levels of oxidant stress, and by elaborating vasoactive cytokines that have downstream effects on renal blood flow and sodium transport. The current review summarizes a set of preclinical experiments that describe the effects of inflammatory cytokines to modulate the hypertensive response through direct actions in the kidney.