EICOSAPENTAENOIC AND DOCOSAHEXAENOIC ACIDS ALTER RAT SPLEEN LEUKOCYTEFATTY-ACID COMPOSITION AND PROSTAGLANDIN E-2 PRODUCTION BUT HAVE DIFFERENT EFFECTS ON LYMPHOCYTE FUNCTIONS AND CELL-MEDIATED-IMMUNITY

Weanling rats were fed on high-fat (178 g/kg) diets which contained 4. 4 g alpha-linolenic (ALA), gamma-linolenic, arachidonic (ARA), eicosap entaenoic (EPA), or docosahexaenoic acid (DHA)/100 g total fatty acids . The proportions of all other fatty acids, apart from linoleic acid, and the proportion of total polyunsaturated fatty acids (PUFA) (approx imately 35 g/100 g total fatty acids) were constant, and the n-6 to n- 3 PUFA ratio was maintained as close to 7 as possible. The fatty acid compositions of the serum and of spleen leukocytes were markedly influ enced by that of the diet. Prostaglandin E-2 production was enhanced f rom leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA-or DHA-fed rats. Replacing dietary ALA with EP A resulted in diminished ex vivo lymphocyte proliferation and natural killer (NK) cell activity and a reduced cell-mediated immune response in vivo. In contrast, replacing ALA with DHA reduced ex vivo lymphocyt e proliferation but did not affect ex vivo NK cell activity or the cel l-mediated immune response in vivo. Replacement of a proportion of lin oleic acid with either gamma-linolenic acid or ARA did not af feet lym phocyte proliferation, NK cell activity, or the cell-mediated immune r esponse. Thus, this study shows that different n-3 PUFA exert differen t immunomodulatory actions, that EPA exerts more widespread and/or str onger immunomodulatory effects than DHA, that a low level of EPA is su fficient to influence the immune response, and that the immunomodulato ry effects of fish oil may be mainly due to EPA.