Immunoglobulin treatment reduces atherosclerosis in apolipoprotein E–/– low-density lipoprotein receptor –/– mice via the complement system

Summary Atherosclerosis is associated with activation of the immune system. Intravenously applied normal polyclonal immunoglobulins (IVIg) have broad therapeutic applications in the treatment of autoimmune and systemic inflammatory diseases. Recently, IVIg have been shown to inhibit atherogenesis in experimental animal models. To investigate the role of the complement system in this process, we used third complement component-deficient  (C3–/–) and control atherosclerosis-prone apolipoprotein E (ApoE) and low-density  lipoprotein  receptor  (LDLR)  double  knock-out  mice  fed  a normal diet. IVIg treatment reduced lesion fraction area in the aortic root of complement-sufficient mice whereas the lesion fraction area of C3–/– mice was not affected. Thus, complement activation plays a role in the anti-atherosclerotic effects of IVIg, possibly by C3-derived fragments generated through Fc-dependent complement activation.