Tumor necrosis factor production by murine resident peritoneal macrophages is enhanced by dietary n−3 polyunsaturated fatty acids

Abstract

Tumor necrosis factor (TNF) is a macrophage derived peptide that has an antitumor action and modulates immune and inflammatory reactions. Dietary fatty acids may modulate TNF production as dietary n−3 polyunsaturated fatty acids suppress human monocyte TNF production, but enhance its secretion by murine peritoneal macrophages. Mice were maintained for 5 weeks on diets containing different amounts of n−3 and n−4 fatty acids. TNF, PGE 2 and 6-keto PGF 1α production was monitored following in vitro stimulation of resident peritoneal macrophages with lipopolysaccharide. Macrophages from mice fed the high n−3 diet produced 8-fold more TNF and half the PGE 2 produced by macrophages from mice on the other diets. Indomethacin caused an increase in the TNF production by macrophages from mice on all diets but macrophages from mice on the high n−3 diet produced more TNF than macrophages from mice on the other diets. Exogenous PGE 2 (100 nM) greatly decreased TNF production by macrophages from mice on all diets, but macrophages from mice on the high n−3 diet secreted 70% more TNF than macrophages from mice fed the other diets, indicating that PGE 2 is only partly responsible for the effects observed. The results show that feeding n−3 polyunsaturated fatty acids may cause enhanced TNF production by resident peritoneal macrophages and that PGE 2 is partly responsible for the effect.