Effect Of Il-6 On Atherosclerotic Lesions And Atp-binding Cassette Transporter A1/g1 Gene And Protein Expression In Apoe-/- Mice

Objective: IL-6 is a pleiotropic cytokine, which is closely related to the development of atherosclerosis. The present study intends to oberseve the effect of IL-6 receptor antagonist tocilizumab on the expression of ABCA1 and ABCG1 and the development of atherosclerosis in icasein-induced chronic inflammation model.Methods: Male apoE-/- mice were randomly divided into four groups, at week 8, blood samples were taken for imflamatory cytokine assays. The mice were treated with or without an intraperitoneal injection of IL-6 receptor antagonist tocilizumab (8mg/kg) weekly for additional 6 weeks, and this was continued after administration of casein or distilled water. At termination, the mice were sacrificed; Enzyme-linked immunosorbent assay was used to exam the plasm cytokine. Plasma triglyceride (TG), total cholesterol (TC), and high density lipoprotein cholesterol (HDL-C) were determined by commercially enzymatic methods. Apolipoprotein A-I (apoA-I) and apoB were measured by immunoturbidimetry. Gene and protein expression was analyzed by real-time quantitative PCR and Western blot, respectively. The Oil red O staining was used to detect the aortic root cross atherosclerotic lesions.Results: Enzyme-linked immunosorbent assay showed that IL-6 receptor antagonist tocilizumab significantly reduce the plasma levels of C-reactive protein, TNF and IL-1 , whlie improve the level of IL-10 in apoE-/- mice. Plasma HDL-C and apoA-I concentrations were markedly increased after tocilizumab treatment then the plasma levels of TG and TCwere reduced..Tocilizumab positively regulated gene expression of ABCA1 and ABCG1 in the aorta, liver, and small intestine. Tocilizumab also promoted ABCA1 protein expression in apoE-/- mice. Furthermore, tocilizumab treatment reduced the atherosclerotic lesions in the aortic root.Conclusion: The IL-6 receptor antagonist tocilizumab inhibits the expression of inflammatory cytokines such as CRP TNF in apoE-/- mice, elevates ABCA1 gene and protein expression in the aorta, liver and small intestine, and shows a strong therapeutic effect on the atherosclerotic lesions in baisic and chronic inflammatory condition.