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 cytoki ne production by macrophages (Mempty sets) have yielded conflicting results . We hypothesised that this may be due to the different capacities of the M empty sets studied commonly (resident, thioglycollate-elicited) to produce prostaglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4) which inhibit and sti mulate, respectively, tumour necrosis factor-alpha (TNF-alpha) and interleu kin-1 beta (IL-1 beta) production. To investigate this, male C57B16 mice we re fed for 6 weeks on a low fat (LF) diet or on high fat diets which contai ned coconut oil (CO), olive oil (OO), safflower oil (SO) or fish oil (FO) a s 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 bo th 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 cel ls 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. I n contrast, resident Mempty sets from mice fed FO showed increased TNF-alph a 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 incr eases production of TNF-alpha by resident Mempty sets, at least in comparis on to some other dietary fats. These results indicate the mechanisms by whi ch dietary fats exert their effects upon pro-inflammatory cytokine producti on are most likely different for resident and inflammatory Mempty sets. (C) 2000 Academic Press.