Alteration of tumor necrosis factor-alpha production by macrophages from mice fed diets high in eicosapentaenoic and docosahexaenoic fatty acids.
Dietary exposure to n-3 fats found in marine fish oils are known to reduce certain inflammatory conditions. Although depressed prostaglandin E2 (PGE2) production is thought to be a major mechanism of the beneficial effects, the direct effects of n-3 fatty acids on inflammatory macrophage function are not well understood. In this study, production of the inflammatory monokine, tumor necrosis factor-alpha (TNF alpha), by isolated murine macrophages was assessed following a 3-week feeding with diets containing either 10% menhaden fish oil as a source of n-3 fatty acids or, as a control and source of n-6 fatty acids, 10% safflower oil. Cultures of peritoneal macrophages from mice fed diets with n-3 fatty acids had more TNF alpha activity 24 hr after in vitro stimulation with bacterial lipopolysaccharide than did macrophages from mice fed the n-6-containing diet. The onset and maximal synthesis of bioactive TNF alpha and down-regulation of messenger RNA for TNF alpha appeared to be similar for the two diets, suggesting that macrophages from mice fed a diet high in n-6 but not n-3 fatty acids were capable of removing active TNF alpha from culture media. Experiments in which PGE2 was added exogenously indicated that the removal of TNF alpha from culture supernatant by macrophages was induced by lower concentrations of PGE2 than that associated with termination of production, and that n-3 fatty acid diets caused a selective loss in the clearance mechanism. These results demonstrate a specific alteration of PGE2-mediated regulation of macrophage-produced TNF alpha by n-3 fatty acids.
Somers
S D
SD
Division of Immunology, James N. Gamble Institute of Medical Research, Cincinnati, Ohio 45319.
Erickson
K L
KL
D000818:Animals; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C033266:Menhaden oil; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D015232:Dinoprostone; D007213:Indomethacin