The Effects of Anti-IL-23p19 Therapy on Atherosclerosis Development in ApoE ^−/− Mice

Abstract

The aim of this study is to detect the dynamic expression of interleukin-23 (IL-23) in ApoE−/− mice at different ages and to further examine the effects of anti-IL-23 therapy on atherosclerosis development. The levels of IL-23 in the sera, aortas, and lymph nodes of ApoE−/− mice were significantly increased compared with those of age-matched controls at 8, 12, 16, 20, and 24 weeks of age. Then, 12-week-old ApoE−/− mice were intraperitoneally injected with anti-IL-23p19 neutralizing antibodies, isotype controls, and phosphate-buffered saline for 8 weeks. The proinflammatory and anti-inflammatory mediators in atherosclerotic aortas, plaque areas, plaque necrotic cores, and the contents of major inflammatory cells in plaques were subsequently determined. The results showed that anti-IL-23p19 treatment significantly decreased the expression of IL-17A, IL-6, and TNF-α in the aortas of ApoE−/− mice, but had no obvious effect on the plaque area, plaque necrotic core, or content of major inflammatory cells in atherosclerotic plaques. Although anti-IL-23p19 therapy reduces the expression of several proinflammatory cytokines, it does not significantly suppress the progression of atherosclerosis in ApoE−/− mice.