The Anti-Atherosclerosis Effect of Anakinra, a Recombinant Human Interleukin-1 Receptor Antagonist, in Apolipoprotein E Knockout Mice

Purpose Interleukin (IL)-1β plays an important role in the atherosclerosis pathogenesis. We aimed to investigate the effect of anakinra, a recombinant human IL-1 receptor antagonist, on the progression of atherosclerosis in apolipoprotein E knockout (ApoE−/−) mice.Methods ApoE−/− mice (8-week male) were treated with saline (control), anakinra 10, 25, and 50 mg/kg, respectively (n = 10 in each group). Mice were fed a standard chow (4 weeks) followed by an atherogenic diet (35kcal% fat, 1.25% cholesterol, 12 weeks). Atheromatous plaques and expression of inflammatory genes and signaling pathways in human umbilical vein endothelial cells (HUVECs), rat aortic smooth muscle cells (RAOSMCs), and 3T3-L1 adipocytes were assessed.Results The plaque size of aortic arch (30.6% and 25.2% at the 25mg/kg and 50mg/kg doses, both P −/− mice and inflammatory genes (IL-1β and IL-6) expressions in anakinra-treated HUVECs and RAOSMCs were suppressed (all P Conclusion IL-1 blockade with anakinra significantly reduced atherosclerotic plaque formation in ApoE−/− mice. Also, anakinra reduced expression of inflammatory genes in endothelial cells, smooth muscle cells, and adipocytes and ameliorated processes involved in vascular remodeling. Anakinra could be a useful component of complementary treatment with standard regimen to reduce the residual cardiovascular risk.