Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

TLDR

Atherosclerosis involves immune activation, with T cells and macrophages infiltrating plaques and autoantibodies to oxidized lipoproteins contributing to disease, and in apo E knockout mice, deficiencies in macrophages, lymphocytes, or interferon‑γ receptors reduce lesion formation. The study aimed to determine whether immune modulation in adult apo E knockout mice influences atherosclerosis development. The authors administered polyclonal intravenous immunoglobulin to 7‑week‑old male apo E knockout mice for five days, then monitored fatty streak development over two months on a cholesterol diet. Intravenous immunoglobulin reduced fatty streaks by 35 % and fibrofatty lesions by 50 %, lowered IgM anti‑oxidized LDL antibodies, inactivated splenic and lymph node T cells, and overall demonstrated that immune modulation can prevent and treat atherosclerosis.

Abstract

Atherosclerosis is associated with immune activation. T cells and macrophages 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 atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-gamma receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects disease development. Injections of 7-wk-old male apo E knockout mice with polyclonal immunoglobulin preparations (ivIg) during a 5-d period reduced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduced by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatment also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibits atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity and/or antibody production. Therefore, immunomodulation may be an effective way to prevent and/or treat atherosclerosis.