Interleukin 17 promotes atherosclerosis and protects against aneurysmal rupture

Abstract

Interleukin 17 (IL17) is a unique cytokine produced by Th17 cells, a novel subset of T lymphocytes distinct from Th1 and Th2 cells. Atherosclerosis and aneurysm formation are inflammatory diseases in which Th1 cytokines play an important role. The role of IL17 in atherosclerosis is poorly defined, however, and its role in aneurysm formation is unknown. We investigated the effect of IL17 on atherosclerosis and aneurysm formation by crossing IL17 and ApoE deficient mice. Mice were then subjected to either 3 months of high fat diet or 4 weeks of high fat diet plus Ang II infusion. Aortic atherosclerosis, as defined as percent lesion area, was reduced in IL17−/−/ApoE−/− mice compared to ApoE−/− controls after 3 months of high fat diet (15% vs 20%, n=11, p=0.03) as well as after 4 weeks of high fat diet plus Ang II infusion (13% vs 21%, n=4–5, p=0.02). High fat diet plus Ang II infusion induced a similar degree of abdominal aortic aneurysm (AAA) formation but a greater incidence of death due to AAA rupture in IL17−/−/ApoE−/− mice compared to ApoE−/− controls (31% vs 7%, n=14–16). Thus, IL17 promoted atherosclerosis but protected against aneurysmal rupture. IL17 could therefore represent a novel therapeutic target for treatment of atherosclerosis but its effect on AAA rupture must be taken into consideration when designing strategies that target IL17. Supported by NIH Grants P01HL58000, R01HL39006, P01HL58000, and ACTSI TL1 RR025010.