Dietary arachidonic acid increases eicosanoid production in the presence of equal amounts of dietary eicosapentaenoic acid.

Previously, we demonstrated that dietary n-3 PUFA (1.5%, w/w) effectively inhibited the production of eicosanoids derived from tissue arachidonic acid (AA) (Whelan et al., 1991). More recently, we also reported that dietary AA (1.0%, w/w) significantly augmented platelet and macrophage eicosanoid production in vitro (Whelan et al., 1993). This present study was designed to investigate the antithetic relationship of dietary AA and EPA on eicosanoid production in vivo. Forty-nine CD-1 male mice were randomly divided into four dietary groups. Identical diets were supplemented with ethyl esters (1.5%, w/w) of the following fatty acids: oleic acid (OA), AA, EPA or AA + EPA (A + E). After four weeks on diet, peritoneal cells were stimulated in vivo with opsonized zymosan and analyzed for eicosanoid production (PGE2, 6-keto-PGF1a, TXB2, LTE4, LTB4, LTE5 and LTB5). The pooled eicosanoid production in the AA group was 41% and 300% higher compared to the OA (control) and EPA groups, respectively. Pooled eicosanoid production in the EPA group was 47% that of the OA group. When equivalent amounts of AA and EPA (AA + EPA) were included in the diet, the pooled eicosanoid production was 29% and 274% higher compared to the OA and EPA groups, respectively. These data demonstrate that dietary AA (1) enhances eicosanoid production in vivo and (2) abrogates virtually all of the effects observed with dietary EPA when both are included in the diet. The clinical implications of dietary AA as modulated by increased eicosanoid production could be significant, particularly when n-3 PUFA are used to reduce eicosanoid-mediated events.