Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction

Hypertension. 2010 Feb;55(2):500-7. doi: 10.1161/HYPERTENSIONAHA.109.145094. Epub 2009 Dec 28.


We have shown previously that T cells are required for the full development of angiotensin II-induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We found that angiotensin II infusion increased IL-17 production from T cells and IL-17 protein in the aortic media. To determine the effect of IL-17 on blood pressure and vascular function, we studied IL-17(-/-) mice. The initial hypertensive response to angiotensin II infusion was similar in IL-17(-/-) and C57BL/6J mice. However, hypertension was not sustained in IL-17(-/-) mice, reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin II infusion. Vessels from IL-17(-/-) mice displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells revealed that IL-17, in conjunction with tumor necrosis factor-alpha, modulated expression of >30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL-17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared with normotensive subjects. We conclude that IL-17 is critical for the maintenance of angiotensin II-induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Atherosclerosis / blood*
  • Atherosclerosis / physiopathology
  • Cells, Cultured
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Models, Animal
  • Female
  • Humans
  • Hypertension / blood*
  • Hypertension / physiopathology
  • Interleukin-17 / blood*
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probability
  • Random Allocation
  • Reference Values
  • T-Lymphocytes / metabolism
  • Vascular Diseases / chemically induced
  • Vascular Diseases / metabolism*


  • Interleukin-17
  • Angiotensin II