INFLUENCE OF FK506 ON EXPERIMENTAL ATHEROSCLEROSIS IN CHOLESTEROL-FEDRABBITS

To investigate the role of activated T lymphocytes in the formation of atherosclerotic lesions, we studied the influence of FK506, an immuno suppressant, on the development of atherosclerosis in cholesterol-fed rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isot onic saline (as the control, n = 12) intramuscularly three times a wee k for 12 weeks. Although FK506 treatment did not affect plasma lipid l evels, it caused an increase in the development of atherosclerotic les ions in a dose-dependent manner. Immunohistochemical analysis of the a orta after 8 weeks on the diet revealed that the ratio of T lymphocyte s to the total number of cells in the plaques decreased significantly in the FK506 treated rabbits compared to the control rabbits. In cultu re, FK506 did not affect smooth muscle cell proliferation and choleste ryl ester formation in the macrophages. In contrast, culture medium fr om lymphocytes stimulated by concanavalin A decreased the accumulation of cholesteryl ester in the macrophages. This effect was inhibited by the culture medium in the presence of FK506. These findings suggest t hat activated T lymphocytes may inhibit intracellular cholesterol accu mulation in atherosclerotic plaque. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.