IMMUNOGLOBULIN TREATMENT REDUCES ATHEROSCLEROSIS IN APO-E KNOCKOUT MICE

Atherosclerosis is associated with immune activation. T cells and macr ophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced at herosclerosis, congenital deficiency of macrophages, lymphocytes, or i nterferon-gamma receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects di sease development. Injections of 7-wk-old male apo E knockout mice wit h polyclonal immunoglobulin preparations (ivIg) during a 5-d period re duced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduc ed by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatmen t also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibi ts atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity a nd/or antibody production. Therefore, immunomodulation may be an effec tive way to prevent and/or treat atherosclerosis.