Laboratorio de Patología Renal y Vascular, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain; Red de Investigación Renal (REDINREN), Instituto de Salud Carlos III, Madrid, Spain.
Renal, Vascular and Diabetes Research Laboratory, Fundación Instituto de Investigación Sanitaria-Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
Nefrologia (Engl Ed). 2021 May-Jun;41(3):244-257. doi: 10.1016/j.nefroe.2021.06.003. Epub 2021 Jul 14.
Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by cells of the immune system, predominantly Th17 and γδ lymphocytes. In this paper, we review the role of IL-17A in the pathogenesis of hypertension and in target organ damage. Preclinical studies in mice have shown that systemic adminstration of IL-17A increases blood pressure, probably by acting on multiple levels. Furthermore, IL-17A plasma concentrations are already elevated in patients with mild or moderate hypertension. Many studies in hypertensive mice models have detected IL-17A-producing cells in target organs such as the heart, vessels and kidneys. Patients with hypertensive nephrosclerosis show kidney infiltration by Th17 lymphocytes and γδ lymphocytes that express IL-17A. In addition, in experimental models of hypertension, the blockade of IL-17A by genetic strategies or using neutralizing antibodies, disminished blood pressure, probablyby acting on the small mesenteric arteries as well as in the regulation of tubule sodium transport. Moreover, IL-17A inhibition reduces end-organs damage. As a whole, the data presented in this review suggest that IL-17A participates in the regulation of blood pressure and in the genesis and maintenance of arterial hypertension, and may constitute a therapeutic target of hypertension-related pathologies in the future.
白细胞介素-17A(IL-17A)是一种由免疫系统细胞产生的促炎细胞因子,主要由 Th17 和 γδ 淋巴细胞产生。在本文中,我们回顾了 IL-17A 在高血压发病机制和靶器官损伤中的作用。在小鼠的临床前研究中,全身给予 IL-17A 可能通过多种途径升高血压。此外,轻度或中度高血压患者的 IL-17A 血浆浓度已经升高。许多高血压小鼠模型研究都在心脏、血管和肾脏等靶器官中检测到了产生 IL-17A 的细胞。高血压肾硬化症患者的肾脏中浸润有表达 IL-17A 的 Th17 淋巴细胞和 γδ 淋巴细胞。此外,在高血压的实验模型中,通过遗传策略或使用中和抗体阻断 IL-17A,可能通过作用于小肠系膜动脉以及调节肾小管钠转运来降低血压。此外,IL-17A 抑制可减少靶器官损伤。综上所述,本文综述的资料表明,IL-17A 参与血压的调节以及动脉高血压的发生和维持,并且可能成为未来与高血压相关病理的治疗靶点。