OBJECTIVE: The potential of the atherogenic human carotid plaque to stimulate the inflammatory process was examined in human monocytes and macrophages, in vitro. METHODS AND RESULTS: Exposure of monocytes to human carotid plaque lipid extract (LE) elevated the transcription level of the proinflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α, by 2.9 and 100.2 fold, respectively (as determined by real time PCR), and induced TNF-α secretion (as measured by enzyme-linked immunosorbent assay). Furthermore, LE caused an increase of 1.3-3.1 fold in the mRNA expression of the proinflammatory factors, IL-1β, IL-6, TNF-α, cyclooxygenase-2 and intercellular adhesion molecule-1, in macrophage-like cells. In order to investigate the proinflammatory components in the extract, two fractions, obtained by silica gel separation of LE, were characterized. The cholesterol-oxysterol rich fraction was found to have the most significant proinflammatory effect. It caused an increase in TNF-α expression in monocytes, and upregulated IL-6, TNF-α, intercellular adhesion molecule-1 and cyclooxygenase 2 by 1.5-2.5 fold in macrophages. The triglyceride fraction had almost no effect on the cells. CONCLUSIONS: The human carotid plaque lipid extract was demonstrated to promote inflammation, in vitro. These data support the atherogenic character of the plaque and imply that its lipid composition may have ramifications on the progress of atherosclerosis.