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Interleukin 17A: Key Player in the Pathogenesis of Hypertension and a Potential Therapeutic Target

  • Inflammation and Cardiovascular Diseases (A Kirabo, Section Editor)
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Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

To summarize key advances in our understanding of the role of interleukin 17A (IL-17A) in the pathogenesis of hypertension and highlight important areas for future research and clinical translation.

Recent Findings

While T helper 17 (Th17) cells are major producers of IL-17A, there are several additional innate and adaptive immune cell sources including gamma-delta T cells, innate lymphoid cells, and natural killer cells. IL-17A promotes an increase in blood pressure through multiple mechanisms including inhibiting endothelial nitric oxide production, increasing reactive oxygen species formation, promoting vascular fibrosis, and enhancing renal sodium retention and glomerular injury. IL-17A production from Th17 cells is increased by high salt conditions in vitro and in vivo. There is also emerging data linking salt, the gut microbiome, and intestinal T cell IL-17A production. Novel therapeutics targeting IL-17A signaling are approved for the treatment of autoimmune diseases and show promise in both animal models of hypertension and human studies.

Summary

Hypertensive stimuli enhance IL-17A production. IL-17A is a key mediator of renal and vascular dysfunction in hypertensive mouse models and correlates with hypertension in humans. Large randomized clinical trials are needed to determine whether targeting IL-17A might be an effective adjunct treatment for hypertension and its associated end-organ dysfunction.

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  1. Gwendolyn K. Davis and Daniel J. Fehrenbach contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Division of Clinical Pharmacology, VUMC, Vanderbilt University, 2215 Garland Avenue, P415D MRB IV, Nashville, TN, 37232, USA

    Gwendolyn K. Davis, Daniel J. Fehrenbach & Meena S. Madhur

  2. Vanderbilt Institute for Infection, Immunology, and Inflammation, Nashville, TN, USA

    Meena S. Madhur

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Davis, G.K., Fehrenbach, D.J. & Madhur, M.S. Interleukin 17A: Key Player in the Pathogenesis of Hypertension and a Potential Therapeutic Target. Curr Hypertens Rep 23, 13 (2021). https://doi.org/10.1007/s11906-021-01128-7

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