Inhibition of IL-17A in atherosclerosis

Abstract Objective To determine the effects of interleukin (IL)-17A inhibition on experimental atherosclerosis. Methods and results ApoE−/− mice were treated with either rat anti-mouse IL-17A, mouse anti-mouse IL-17A or isotype-matched control antibodies for 12 weeks ( n = 8–10 per group). Ldlr−/− mice were transplanted with IL-17A-deficient or wild type bone marrow ( n = 8 per group). Rat anti-mouse IL-17A treatment obviously reduced plaque size by 43% ( p < 0.01) without evidence of reduced IL-17A signaling. In contrast, mouse anti-mouse IL-17A treatment and IL-17A deficiency in bone marrow cells did not alter lesion size despite significant reduction of IL-17A production. Conclusions Inhibition of IL-17A signaling does not alter lesion development in Th1-biased C57BL/6 ApoE−/− and Ldlr−/− mice with already low levels of IL-17A production. Alteration of lesion development after repeated injections of rat anti-mouse IL-17A antibody in ApoE−/− mice could not be attributed to blockade of IL-17A signaling.