INTRAVENOUS-INFUSION OF N-3 POLYUNSATURATED FATTY-ACIDS

Dietary supplementation with n-3 polyunsaturated fatty acids (PUFA) is regarded as beneficial for the prevention and treatment of atherosclerosis and thrombosis and chronic inflammatory diseases like rheumatoid arthritis and psoriasis. It may be possible to treat some acute diseases like acute myocardial infarction or acute rejection of grafted organs if it is possible to make n-3 PUFA take effect quickly (in hours instead of days). Three sets of experiments were done. In Experiment 1, emulsion of trieicosapentaenoyl-glycerol (EPA-TG) and tridocosahexaenoyl-glycerol was infused through rabbit ear veins, and the leukotriene B4/B-5 production from Polymorphonuclear leukocytes was measured at different time points by high-performance liquid chromatography. In Experiment 2, delayed type hypersensitivity (DTH) of mice was measured with sheep red blood cells as an antigen. Pure n-3 PUFA emulsions or a control solution were infused through tail veins just before the second challenge of the antigen. DTH was measured 24 hr after the second challenge. In Experiment 3, human natural killer cell activity was measured using K562 target cells before and after the infusion of pure EPA-TG emulsion to an antecubital vein. Leukotriene B4 production by rabbit polymorphonuclear leukocytes was depressed by 40% by EPA-TG infusion. DTH was suppressed almost completely by n-3 PUFA infusion. Natural killer cell activity was suppressed almost completely by EPA-TG infusion in 8 hr. DTH, natural killer cell activity, and leukotriene B4 production are probably related to acute rejection of grafted organs. Because these parameters can be modified in a few hours by the infusion of n-3 PUFA emulsions, in marked contrast to the case with dietary n-3 PUFA, they may be beneficial for the prevention of acute rejection.