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Dietary balance of long-chain fatty acids may influence processes involving leukocyte-endothelial interactions, such as atherogenesis and inflammation, that involve increased endothelial expression of leukocyte adhesion molecules, or endothelial activation. We compared the ability of various saturated, monounsaturated, and polyunsaturated fatty acids to modulate endothelial activation. Consumption of the n−3 fatty acid docosahexaenoic acid (DHA; 22:6n−3) reduced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1), E-selectin, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), and IL-8 in response to IL-1, IL-4, tumor necrosis factor, or bacterial endotoxin, with a half-maximal inhibitory concentration (IC₅₀) of 1–25 μmol, ie, in the range of nutritionally achievable plasma concentrations. The magnitude of this effect paralleled its incorporation into cellular phospholipids. DHA also …