Activation state alters the effect of dietary fatty acids on pro-inflammatory mediator production by murine macrophages

Studies investigating the effect of dietary fats on pro-inflammatory cytokine production by macrophages (Mempty sets) have yielded conflicting results. We hypothesised that this may be due to the different capacities of the Mempty sets studied commonly (resident, thioglycollate-elicited) to produce prostaglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4) which inhibit and stimulate, respectively, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) production. To investigate this, male C57B16 mice were fed for 6 weeks on a low fat (LF) diet or on high fat diets which contained coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) as the main fat source. Production of TNF-alpha, IL-1 beta, PGE(2) and LTB4 by lipopolysaccharide-stimulated resident and thioglycollate-elicited (i.e. inflammatory) peritoneal Mempty sets was measured. PGE(2) production by both inflammatory and resident Mempty sets was significantly decreased by FO feeding, FO also decreased LTB4 production by resident Mempty sets compared with LF feeding. Production of both cytokines by inflammatory Mempty sets decreased with increasing unsaturation of the high fat diets, such that cells from FO-fed mice showed significantly decreased production of TNF-alpha and IL-1 beta compared to those from mice fed on each of the other diets. In contrast, resident Mempty sets from mice fed FO showed increased TNF-alpha production compared to those from CO-fed mice, Thus, FO feeding decreases production of TNF-alpha and IL-1 beta by inflammatory Mempty sets and increases production of TNF-alpha by resident Mempty sets, at least in comparison to some other dietary fats. These results indicate the mechanisms by which dietary fats exert their effects upon pro-inflammatory cytokine production are most likely different for resident and inflammatory Mempty sets. (C) 2000 Academic Press.