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Front. Pharmacol. | doi: 10.3389/fphar.2019.01015

IL-17A participates in renal inflammation associated to experimental and human hypertension

 Macarena Orejudo1,  Raúl R. Díez1, Raquel Rodrigues-Díez2, Ana García-Redondo2, Laura Santos-Sánchez1,  Alberto Ortiz1,  Rafael Selgas3,  Sergio A. Mezzano4, Carolina Lavoz4 and  Marta Ruiz-Ortega1*
  • 1Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Spain
  • 2Pharmacology, Autonomous University of Madrid, Spain
  • 3University Hospital La Paz Research Institute (IdiPAZ), Spain
  • 4Faculty of Medicine, Austral University of Chile, Chile

Hypertension is now considered as an inflammatory disease and the kidney is a key end-organ target. Experimental and clinical studies suggest that IL-17A is a promising therapeutic target in immune and chronic inflammatory diseases, including hypertension and kidney disease. Elevated circulating IL-17A levels have been observed in hypertensive patients. Our aim was to investigate whether chronically elevated circulating IL-17A levels could contribute to kidney damage, using a murine model of systemic IL-17A administration. Blood pressure increased after 14 days of IL-17A-infusion in mice when compared to control mice, and this was associated to kidney infiltration by inflammatory cells, including CD3+ and CD4+ lymphocytes and neutrophils. Moreover, proinflammatory factors and inflammatory-related intracellular mechanisms were upregulated in kidneys from IL-17A-infused mice. In line with these findings, in the model of Angiotensin II infusion in mice, IL-17A blockade, using an anti-IL17A neutralizing antibody, reduced kidney inflammatory cell infiltrates and chemokine overexpression. In kidney biopsies from patients with hypertensive nephroesclerosis IL-17A positive cells, mainly Th17 and γδ T lymphocytes, were found. Overall, the results support a pathogenic role of IL-17A in hypertensive kidney disease-associated inflammation. Therapeutic approaches targeting this cytokine should be explored to prevent hypertension-induced kidney injury.

Keywords: IL-17A, Hypertension, IL-17A neutralization, Inflammation, Kidney

Received: 01 Mar 2019; Accepted: 09 Aug 2019.

Copyright: © 2019 Orejudo, Díez, Rodrigues-Díez, García-Redondo, Santos-Sánchez, Ortiz, Selgas, Mezzano, Lavoz and Ruiz-Ortega. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Marta Ruiz-Ortega, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, 28040, Madrid, Spain, marta.ruiz.ortega@uam.es