Dietary fatty acids influence the production of Th1-but not Th2-type cytokines

C57B16 mice were fed for 6 weeks on a low-fat diet or on high-fat diets con taining coconut oil (rich in saturated fatty acids), safflower oil [rich in n-6 polyunsaturated fatty acids (PUFAs)], or fish oil (rich in n-3 PUFAs) as the main fat sources, The fatty acid composition of the spleen lymphocyt es was influenced by that of the diet fed, Thymidine incorporation into con canavalin A-stimulated spleen lymphocytes and interleukin (IL)-2 production were highest after feeding the: coconut oil diet, Interferon (IFN)-gamma p roduction was decreased by safflower oil or fish oil feeding, IL-4 producti on was not significantly affected by diet, although production was lowest b y lymphocytes from fish oil-fed mice. The ratio of production of Th1- to Th 2-type cytokines (determined as the IFN-gamma /IL-4 ratio) was lower for ly mphocytes from mice fed the safflower oil or fish oil diets, After 4 h of c ulture, IL-2 mRNA levels were higher in cells from mice fed coconut oil, an d IFN-gamma mRNA levels were higher in cells from mice fed coconut oil or s afflower oil, After 8 h of culture, IL-2, IFN-gamma, and IL-4 mRNA levels w ere lowest in cells from mice fed fish oil, The ratio of the relative level s of IFN-gamma mRNA to IL-4 mRNA was highest in cells from mice fed coconut oil and was lowest in cells of mice fed fish oil, The influence of individ ual fatty acids on IL-2 production by murine spleen lymphocytes was examine d in vitro. Although all fatty acids decreased IL-2 production in a concent ration-dependent manner, saturated fatty acids were the least potent and n- 3 PUFAs the most potent inhibitors, with n-6 PUFAs falling in between in te rms of potency, Tt is concluded that saturated fatty acids have minimal eff ects on cytokine production, in contrast, PUFAs act to inhibit production o f Th1-type cytokines with little effect on Th2-type cytokines; n-3 PUFAs ar e particularly potent, The effects of fatty acids on cytokine production ap pear to be exerted at the level of gene expression.