The mechanisms by which dietary fatty acids can modulate atherogenesis and inflammation are poorly understood. Induction in endothelial cells of adhesion molecules for circulating leukocytes and of inflammatory mediators by cytokines probably contributes to the early phases of atherogenesis and inflammation. We report here that incorporation into cellular lipids of docosahexaenoic acid (DHA), a specific fatty acid of the aZ family, decreases cytokine-induced expression of endothelial leukocyte

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... dhesion molecules, secretion of inflammatory mediators, and leukocyte adhesion to cultured endothelial cells. DHA, but not eicosapentaenoic acid, decreased in a dose-and time-dependent fashion the expression of vascular cell adhesion molecule 1 (VCAM-1) induced by interleukin (IL)-1, tumor necrosis factor (TNF), IL-4, or bacterial lipopolysaccharide, with half-maximum inhibition at <10 jimol/L. This reduction required prolonged (24-to 96hour) exposure of endothelial cells to DHA and correlated D ietary long-chain omega-3 polyunsaturated fatty acids (CJ3 FA) modulate a wide range of cell responses. 13 Epidemiological studies suggest an inverse relation between intake of w3 FA and the incidence of cardiovascular disease, 412 at least in part because of reduced atherosclerosis. 13 Consumption of o>3 FA diminishes atherogenesis in nonhuman primates 1415 as well as in other animal species (reviewed in References 1 and 2). In addition to atherothrombotic diseases, epidemiological studies demonstrate an inverse relation between dietary intake of w3 FA and some inflammatory/immune diseases such as psoriasis, bronchial asthma, and thyrotoxicosis. 4 Both atheroma formation and inflammation require the adhesion of circulating leukocytes to the endothelium and their subsequent transendothelial migra-