Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice.

Abstract

BACKGROUND: Although immunoglobulin treatment, beginning simultaneously with the initiation of atherosclerosis, suppresses experimental atherosclerosis in apolipoprotein E-deficient mice, it remains unclear whether the treatment at a subsequent stage of atherosclerosis would be effective. METHODS AND RESULTS: Experimental atherosclerosis was induced in mice fed a high-fat diet containing 0.3% cholesterol. After confirming the presence of atherosclerotic lesions at 11 weeks, the mice were treated with an intraperitoneal injection of either intact type of immunoglobulin or F(ab')2 fragments of immunoglobulin (both, 1 g.kg-1.day-1) on alternate days over 4 weeks. Fatty streak lesion was suppressed by intact immunoglobulin administration, but not by F(ab')2 fragments of immunoglobulin. Immunohistochemical analysis showed that macrophage and CD4+ T-cell accumulation in the fatty streak lesion was suppressed in mice that received intact immunoglobulin but not in those that received F(ab')2 fragments. CONCLUSIONS: Immunoglobulin treatment, even at a later stage of atherosclerosis, suppresses the development of lesions associated with the reduced expression of immune-activated cells in fatty streak plaques, demonstrating the benefits of immunoglobulin therapy for prevention of atherosclerosis.