Abstract 759: Inhibition Of Pro-inflammatory Cytokine Il-17 Reduces Atherosclerotic Lesion Development In Apo E −/ − Mice
Atherosclerotic plaque typically contains infiltrates of activated macrophages and T cells. In human carotid artery plaques, we previously showed the presence of IL-17 producing T cells (Th17) and IL-23. Effects of inhibition of the pro-inflammatory Th1 cytokine IL-17 on atherosclerosis development was studied in a rodent model. 25 female ApoE −/ − mice fed a normal diet were treated with a specific blocking antibody against IL-17 for 12 weeks (100 μg intraperitoneally once per week). For analysis, aortic root was embedded in OCT and serially cryosectioned in 5μm intervals; distal aorta was snap frozen for mRNA analysis. Sections every 75μm were stained with Oil RedO, the lesion area was quantified using PC-based image analysis. In IL-17 treated mice no changes in LDL cholesterol and anti-ox LDL antibodies were seen. Subsets of immune cells, surface marker expression and fraction of regulatory T cells in peripheral blood / spleen were unchanged. Inhibition of IL-17 markedly reduced atherosclerotic plaque volume by 65% (p=0.004) and fractional stenosis by 68% (p=0.01). Immunohistochemistry revealed significant reduction of cellular infiltration by T cells and macrophages in atherosclerotic lesions. By quantitative RT-PCR, significantly reduced expression was shown (among others) for CD3ϵ, egr-1, Akt and RANKL (all p< 0.01). Functional blockade of Th1 cytokine IL-17 reduces atherosclerotic lesion development in an established animal model without major derangement of peripheral cellular immunity. Our findings suggest a relevant role for IL17-producing T cells in atherosclerosis warranting further study of pathogenic mechanisms and therapeutic potential.