The effects of dietary n-3 polyunsaturated fatty acids and cyclic AMP-elevating agents on tumor necrosis factor production by murine-resident and thioglycollate-elicited peritoneal macrophages

Abstract

Tumor-necrosis factor (TNF), prostaglandin (PG) E 2, and 6-keto PGF 1a production by peritoneal macrophages was monitored following incubation with various cAMP-elevating agents and stimulation with lipopolysaccharide (LPS). Resident and thioglycollate (TG)-elicited macrophages were obtained from mice maintained for 4 weeks on diets containing 3 wt % n-6 fatty acids; 1.0 wt % n-3 polyunsaturated fatty acids (PUFA) + 1.5 wt % n-6 fatty acids; or 1.5 wt % n-3 PUFA + 1.5 wt % n-6 fatty acids. Increasing the n-3 PUFA content of the diet increased TNF production and decreased PG production by the resident peritoneal macrophages. The cAMP analog, 8-br cAMP, and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, decreased TNF production by resident peritoneal macrophages from mice consuming all diets. The adenylate cyclase (AC) activators, cholera toxin and forskolin, only decreased TNF production by resident macrophages from mice consuming the higher level of n-3 PUFA. The effects of dietary n-3 PUFA on TNF production by the resident peritoneal macrophages appear not to be mediated by cAMP, as the cAMP-elevating agents did not eliminate the dietary effects on TNF production. TG-elicited macrophages produced more TNF and less PG than the resident peritoneal macrophages. Adding n-3 PUFA to the diet did not affect TNF nor PG production by TG-elicited macrophages. The cAMP-elevating agents decreased TNF production by TG-elicited macrophages from mice consuming diets with or without n-3 PUFA. These findings show that cAMP-elevating agents decrease TNF production by both resident and elicited peritoneal macrophages, but may not be involved in the effect of n-3 PUFA on TNF production by the resident peritoneal macrophages.