Abstract 006: Distinct and Overlapping Roles of Cytokines IL-17A and IL-17F in Angiotensin II-induced Hypertension and End-organ Injury
Recently, interleukin-17A (IL-17A) has been found to contribute to the renal and vascular dysfunction associated with hypertension, but the mechanisms involved are unknown. We and others found that IL-17F is upregulated in IL-17A deficient mice, suggesting a compensatory response. The goal of the present study was to determine the role of IL-17F in hypertension and the effect of IL-17A or IL-17F neutralization on blood pressure and renal/vascular inflammation. Twelve-week-old male C57BL/6J mice received angiotensin II (Ang II) (490 ng/kg/min, s.c. via 4 wk-osmotic minipump). After 2 weeks, the systolic blood pressure as measured by tail-cuff was 179.4 ± 3.7 mmHg, n=33. Mice were then randomly assigned to one of four treatment groups: (1) Mouse anti-IL-17A; (2) Rat anti-IL-17F; (3) Mouse IgG1 control; (4) Rat IgG1 control. Mice were injected intraperitoneally with 100 μg of antibodies twice weekly during the remaining 2 weeks of Ang II infusion. The administration of anti-IL-17A, but not anti-IL-17F, improved Ang II-induced hypertension (166.5 ± 7.4 mmHg, n=10 vs 181.8 ± 8.6 mmHg, n=7 respectively). Interestingly, both anti-IL-17A and anti-IL-17F blunted the increase in aortic and renal total leukocyte infiltration as quantified by flow cytometry in both organs (Fig. 1a). In addition, both treatments attenuated the increase in glomerular injury as monitored by albuminuria measurement (ELISA) during the Ang II infusion period (Fig. 1b). In conclusion, IL-17F neutralization does not lower blood pressure in response to Ang II, but both IL-17A and IL-17F are pro-inflammatory and orchestrate a major role in the end-organ damage associated with Ang II-induced hypertension.
Author Disclosures: M.A. Saleh: None. A.E. Norlander: None. D.G. Harrison: None. M.S. Madhur: None.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2015 by American Heart Association, Inc.