Immune-modulation by polyclonal IgM treatment reduces atherosclerosis in hypercholesterolemic apoE−/− mice

Abstract Objective Gamma-globulin treatment reduces experimental atherosclerosis by modulating immune function; however the effect of IgM on atherosclerosis is not known. We investigated the effect of serum-derived, non-immune polyclonal IgM (Poly-IgM) on atherosclerosis in mice with advanced disease and also assessed its immune-modulatory effects. Methods and results Aortic atherosclerosis was assessed in apoE−/− mice fed atherogenic diet starting at 6 weeks of age. In addition, mice were also subjected to perivascular cuff injury to the carotid artery at 25 weeks of age to induce accelerated atherosclerosis. At the time of injury, the mice were treated weekly with a commercially available Poly-IgM (0.4 mg/mouse) or PBS for 4 weeks and euthanized at 29 weeks of age. Poly-IgM reduced aortic atherosclerosis, and reduced lesion size in the aortic sinus and injured carotid artery, without significant changes in serum cholesterol levels. Poly-IgM treatment was associated with increased anti-oxLDL IgG titers and a reduction in the % splenic CD4+ T cells compared to controls. The splenic CD4+ T cell cultured from the Poly-IgM treated mice had reduced proliferation in vitro compared with controls. Conclusion Poly-IgM treatment reduced aortic and accelerated carotid atherosclerosis in apoE−/− mice in association with increased anti-oxLDL IgG titers, and reduced number and proliferative function of splenic CD4+ T cells. Our study identifies a novel athero-protective and immunomodulatory role for non-immune polyclonal IgM.