EFFECT OF N-6 AND N-3 FATTY-ACIDS ON THE PROLIFERATION OF HUMAN-LYMPHOCYTES AND THEIR SECRETION OF TNF-ALPHA AND IL-2 INVITRO

Lymphocytes, tumor necrosis factor (TNF) and interleukin-2 (IL-2) participate in inflammation, whereas n-3 and n-6 fatty acids possess anti-inflammatory effects. Hence, we studied the effects of n-3 and n-6 fatty acids on lymphocyte proliferation and their ability to produce TNF and IL-2 in vitro. Alpha linolenic acid (ALA, 18:3, n-3), dihomogamma linolenic acid (DGLA, 20:3, n-6) and arachidonic acid (AA, 20:4, n-6) were found to have weak inhibitory action on the proliferation of human lymphocytes compared to linoleic acid (LA, 18:2, n-6), gamma linolenic acid (GLA, 18:3, n-6), eicosapentaenoic acid (EPA, 20:5.n-3), and docosahexaenoic acid (DHA, 22:6, n-3). The growth inhibitory actions of the fatty acids was blocked by Vitamin E and superoxide dismutase but not by cyclo-oxygenase (CO) and lipoxygenase (LO) inhibitors indicating a role for free radicals in this process. On the other hand, at 10-mu-g/ml of fatty acid concentration ALA, was most effective in supressing the secretion of TNF-alpha followed by LA and GLA, while at 20-mu-g/ml concentration DHA was the most potent fatty acid in suppressing TNF-alpha secretion followed by ALA, LA and DGLA. With regard to IL-2 secretion, GLA at 10-mu-g/ml concentration was found to be the most effective inhibitor. Of all the fatty acids tested, ALA exhibited least cytotoxicity to lymphocytes with maximum inhibitory action on TNF with lesser effect on IL-2 (TNF > IL-2) production. The effect of fatty acids on TNF and IL-2 production, unlike their inhibitory action on lymphocyte proliferation, was not blocked by either anti-oxidants or by CO and LO inhibitors. These results suggest that fatty acids are able to bring about their anti-inflammatory actions, at least, in part by their inhibitory action on lymphocyte proliferation and TNF and IL-2 production.