Dietary n-3 Fatty Acids Alter Murine Peritoneal Macrophage Cytotoxicity

Abstract

Male CD-I mice were fed diets containing 10 wt% fat composed of a constant amount of n-6 polyunsaturated fatty acids (PUFA; safflower oil, 1.5 wt%) and increasing levels of n-3 PUFA (up to 1.5 wt%); the remaining fat was a 50:50 mixture of tripalmitin and triolein. Four days prior to sacrifice, the animals were injected intraperitoneally with sterile thioglycollate. Peritoneal macrophages were analyzed for phospholipid fatty acids, prostaglandin E₂ (PGE₂) synthesis and cytotoxicity towards L929 target cells. Increasing dietary n-3 PUFA increased macrophage phospholipid n-3 PUFA from 4.4 to 11.0 mol% with a concomitant decline in n-6 PUFA from 15.5 to 10.9 mol%, and PGE₂ synthesis declined from 2.6 to 1.5 pmol/million cells in thioglycollate-elicited macrophages. Macrophage cytotoxicity toward target L929 cells declined by approximately 50% with increasing n-3 PUFA concentration.

Immunomodulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

“…Dietary FO has been reported to significantly suppress lysis of target tumour cells by mouse elicited peritoneal macrophages (for references, see Table 3). The target cell lines used in these studies are sensitive to killing by tumour necrosis factor (TNF)-a (L929 cells; Black & Kinsella, 1993) or NO (P815 cells; Somers et al 1989;Hubbard et al 1994). Thus, the suppressed macrophage-mediated cytolysis observed after FO feeding is consistent with the decreased production of NO (see Table 3) and TNF (see Tables 4 and 5 ) reported from some studies.…”

Dietary fats affect macrophage‐mediated cytotoxicity towards tumour cells

“…A number of studies have previously investigated the effect of dietary fats on TNF‐α and nitric oxide production by rodent macrophages (see Introduction for references), but few have investigated macrophage‐ mediated cytotoxicity. For example, although there are many studies of the effects of FO on mediator production, to our knowledge only two studies have investigated the effect of FO on macrophage‐mediated killing of L929 29 , 36 or P815 cells 28 , 37 . One of the studies that investigated killing of L929 cells did not measure TNF‐α production, 36 while one of the studies that investigated killing of P815 cells did not measure nitric oxide production 37 .…”

“…However, there are considerable discrepancies in the literature: several studies report that dietary FO results in enhanced production of TNF 12 , 22 , 23 , 24 , 25 , 26 , 27 , 28 and nitric oxide 12 , 29 , 30 by macrophages ex vivo , while other studies report that FO decreases production of TNF 29 , 31 , 32 , 33 , 34 and nitric oxide 34 , 35 by such cells. A limited number of studies have investigated the cytotoxicity of macrophages following dietary lipid manipulation: FO feeding has been shown to decrease macrophage‐mediated killing of L929 cells 29 , 36 and P815 cells, 28 , 37 compared with feeding certain other diets. Because these cells are killed by TNF‐α and nitric oxide, respectively, these observations suggest that FO decreases production of TNF‐α and nitric oxide by macrophages.…”

Important Differences Exist in the Dose–Response Relationship between Diet and Immune Cell Fatty Acids in Humans and Rodents

“…Interestingly, resident M/ from the peritoneum of rodents accumulate more EPA than human monocytes and elicited M/ rodents at each level of dietary EPA intake. Yet, only a single research group directly compared the response of resident and elicited M/ to diet n-3 PUFA treatment [33]. Those data, however, follow the same general pattern illustrated in Fig.…”