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. [Copyright &y& Elsevier]