Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.
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.
Nicoletti
A
A
Center for Molecular Medicine, Karolinska Institute, S-17176 Stockholm, Sweden.
Kaveri
S
S
Caligiuri
G
G
Bariéty
J
J
Hansson
G K
GK
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency*; D001161:Arteriosclerosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000276:immunology; D004032:Diet; D006651:Histocytochemistry; D007074:Immunoglobulin G / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D008077:Lipoproteins, LDL / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001057:Apolipoproteins E; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein