ACTIVATION STATE ALTERS THE EFFECT OF DIETARY FATTY ACIDS ON PRO-INFLAMMATORY MEDIATOR PRODUCTION BY MURINE MACROPHAGES

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2000-09, Vol.12 (9), p.1374-1379
• Main Authors: Wallace, Fiona A, Miles, Elizabeth A, Calder, Philip C
• Format: Article
• Language: English
• Subjects: Animals; Coconut Oil; Cytokines - biosynthesis; Diet; Diet, Fat-Restricted; Dinoprostone - biosynthesis; Enzyme-Linked Immunosorbent Assay; Fatty Acids - metabolism; Fatty Acids - pharmacology; Fish Oils - pharmacology; Interleukin-1 - biosynthesis; Leukotriene B4 - biosynthesis; Lipopolysaccharides - pharmacology; macrophage/inflammation/cytokine/polyunsaturated fatty acid/fish oil; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Olive Oil; Peritoneum - metabolism; Plant Oils - pharmacology; Safflower Oil - pharmacology; Thioglycolates - pharmacology; Tumor Necrosis Factor-alpha - biosynthesis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2000.0735

Studies investigating the effect of dietary fats on pro-inflammatory cytokine production by macrophages (MØs) have yielded conflicting results. We hypothesised that this may be due to the different capacities of the MØs studied commonly (resident, thioglycollate-elicited) to produce prostaglandin E2(PGE2) and leukotriene B4(LTB4) which inhibit and stimulate, respectively, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production. To investigate this, male C57Bl6 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-α, IL-1β, PGE2and LTB4by lipopolysaccharide-stimulated resident and thioglycollate-elicited (i.e. inflammatory) peritoneal MØs was measured. PGE2production by both inflammatory and resident MØs was significantly decreased by FO feeding. FO also decreased LTB4production by resident MØs compared with LF feeding. Production of both cytokines by inflammatory MØs decreased with increasing unsaturation of the high fat diets, such that cells from FO-fed mice showed significantly decreased production of TNF-α and IL-1β compared to those from mice fed on each of the other diets. In contrast, resident MØs from mice fed FO showed increased TNF-α production compared to those from CO-fed mice. Thus, FO feeding decreases production of TNF-α and IL-1β by inflammatory MØs and increases production of TNF-α by resident MØs, 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 MØs.