Omega-3 Fatty Acid Lipid Emulsion Reduces LPS-Stimulated Macrophage TNF-α Production

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Abstract
Background: Omega-3 (ω-3) fatty acids (FA), specifically eicosapentaenoic acid (EPA), attenuate cytokine-mediated inflammation. Currently, in the United States, there is no commercial source of ω-3 lipid for clinical use. A clinically used European lipid emulsion, Omegaven®, has been shown to have beneficial antiinflammatory effects; however, the mechanisms of its action are not well defined. In the present work, this ω-3 FA emulsion has been evaluated in order to define its effects on TNF-α production in a model of LPS-stimulated macrophages. Materials and Methods: RAW 264.7 cells (1 × 106 cell/well) were incubated with DMEM, Omegaven®, or an isoenergetic ω-6 lipid emulsion, Lipovenos® for 4 h. Cells were washed and then stimulated with LPS (1 μg/mL) or media alone for 3 h. Plate well supernatants were collected and assayed for TNF-α production by ELISA. Statistical analysis was performed by ANOVA and post-hoc analyses; the significance was defined as p < 0.05. Results: Unstimulated RAW cell TNF-α production was similar in all groups and < 60 pg/mL. Lipovenos® pretreatment did not alter TNF-α production from that of baseline compared to LPS-stimulated cells. Four-hour Omegaven® pretreatment significantly reduced TNF-α production in LPS-stimulated cells, with a 46% reduction in TNF-α from baseline observed. Conclusion: Four-hour ω-3 FA emulsion pretreatment significantly attenuated LPS-stimulated macrophage TNF-α production. These data support the contention that antiinflammatory effects of ω-3 FA occur at least in part through the inhibition of macrophage TNF-α production in response to endotoxin. Further studies to define the antiinflammatory mechanisms of ω-3 FA on macrophages are warranted. The availability of Omegaven® as an experimental treatment and Lipovenos® as an equivalent control will be useful for future studies.

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