Increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio increases tumor necrosis factor production by murine resident peritoneal macrophages without an effect on elicited peritoneal macrophages.
Tumor necrosis factor (TNF), prostaglandin (PG) E2 and 6-keto-PGF1 alpha production by murine peritoneal macrophages was monitored following in vitro stimulation with lipopolysaccharide. Macrophages were obtained from mice fed diets containing increasing ratios of (n-3) to (n-6) fatty acids by addition of (n-3) polyunsaturated fatty acids (PUFA) to the (n-6) fatty acids in the diet, or by substituting (n-3) PUFA for the (n-6) fatty acids in the diet. Increasing the dietary (n-3) to (n-6) fatty acid ratio from 0 to 1 increased both cell-associated and secreted TNF production by resident peritoneal macrophages but did not affect TNF production by macrophages elicited with Complete Freund's Adjuvant (CFA). With increasing dietary (n-3): (n-6) ratio there was a decrease in the prostaglandin production by resident peritoneal macrophages, which may partly explain the increased TNF production. The CFA-elicited macrophages produced less prostaglandin than the resident macrophages, and the lower prostaglandin production may partly explain the lack of effect of dietary (n-3) PUFA on TNF production by CFA-elicited macrophages. Increasing the TNF production by resident macrophages with dietary (n-3) PUFA may be beneficial in enhancing antitumor actions and antipathogenicity; by not increasing the high TNF production of inflammatory macrophages, (n-3) PUFA may protect against undesirable systemic inflammatory effects of overproduction.
Hardardóttir
I
I
Lipids Research Laboratory, Cornell University, Ithaca, NY 14853.
Kinsella
J E
JE
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D002452:Cell Count; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D015232:Dinoprostone / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D005260:Female; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010537:Peritoneum; D010743:Phospholipids / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D008070:Lipopolysaccharides; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone