Dietary fats affect macrophage-mediated cytotoxicity towards tumour cells

In the present study, the effects of feeding mice diets of different fatty acid compositions on the production of TNF-alpha and nitric oxide by lipopo lysaccharide-stimulated peritoneal macrophages and on macrophage-mediated c ytotoxicity towards L929 and P815 cells were investigated, C57B16 mice were fed on a low-fat (LF) diet or on high-fat diets (21% fat by weight), which included coconut oil (CO), olive oil (OO), safflower on (SO) or fish oil ( FO) as the principal fat source. The fatty acid composition of the macropha ges was markedly influenced by that of the diet fed. Lipopolysaccharide (LP S)-stimulated macrophages from FO-fed mice showed significantly lower produ ction (up to 80%) of PGE, than those from mice fed on each of the other die ts. There was a significant positive linear correlation between the proport ion of arachidonic acid in macrophage lipids and the ability of macrophages , to produce PGE(2). Lipopolysaccharide-stimulated TNF-cr production by mac rophages decreased with increasing unsaturated fatty acid content of the di et (i.e. FO < SO < OO < CO < LF). Macrophages from FO-fed mice showed signi ficantly lower production of TNF-alpha than those from mice fed on each of the other diets. Nitrite production was highest for LPS-stimulated macropha ges from mice fed on the LF diet. Macrophages from FO-fed mice showed signi ficantly higher production of nitrite than those from mice fed on the OO an d SO diets. Compared with feeding the LF diet, feeding the CO, OO or SO die ts significantly decreased macrophage-mediated killing of P815 cells (kille d by nitric oxide). Fish oil feeding did not alter killing of P815 cells by macrophages, compared with feeding the LF diet; killing of P815 cells was greater after FO feeding than after feeding the other high fat diets. Compa red with feeding the LF diet, feeding the OO or SO diets significantly decr eased macrophage-mediated killing of L929 cells (killed by TNF). Coconut oi l or FO feeding did nut alter killing of L929 cells by macrophages, compare d with feeding the LF diet. It is concluded that the type of fat in the die t affects macrophage composition and alters the ability of macrophages to p roduce cytotoxic and immunoregulatory mediators and to kill target tumour c ells.