Eicosapentaenoic and docosahexaenoic acids alter rat spleen leukocyte fatty acid composition and prostaglandin E2 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), eicosapentaenoic (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) (approximately 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 influenced by that of the diet. Prostaglandin E2 production was enhanced from leukocytes from rats fed the ARA-rich diet and was decreased from leukocytes from the EPA- or DHA-fed rats. Replacing dietary ALA with EPA 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 lymphocyte proliferation but did not affect ex vivo NK cell activity or the cell-mediated immune response in vivo. Replacement of a proportion of linoleic acid with either gamma-linolenic acid or ARA did not affect lymphocyte proliferation, NK cell activity, or the cell-mediated immune response. Thus, this study shows that different n-3 PUFA exert different immunomodulatory actions, that EPA exerts more widespread and/or stronger immunomodulatory effects than DHA, that a low level of EPA is sufficient to influence the immune response, and that the immunomodulatory effects of fish oil may be mainly due to EPA.