Effects of long-term oral administration of arachidonic acid and docosahexaenoic acid on the immune functions of young rats.

Natural killer (NK) cells have many functional activities, including cytotoxicity and the capacity to produce cytokines and chemokines. NK cell activity is regulated partly by eicosanoids, which are produced from arachidonic acid (ARA) and eicosapentaenoic (EPA) acid. In this study, we investigated the effects of long-term therapy with ARA or docosahexaenoic acid (DHA) on the cytotoxic effects of the NK cells of young rats, which were fed on a nonfish oil diet for two generations. Control oil, ARA (240 mg/kg BW/day) or DHA (240 mg/kg BW/day) were orally administrated to the rats for 13 weeks before determining the cytotoxic activity of NK cells from the spleen against YAC-1 mouse lymphoma cell line, as well as the plasma levels of docosanoids or eicosanoids and inflammatory cytokines. Long-term ARA administration significantly suppressed the cytotoxic activity of NK cells. Moreover, ARA administration significantly increased the plasma levels of ARA, prostaglandin (PG) E2, and PGD2. However, DHA administration did not produce any different effects compared with those in the control rats. Furthermore, the inflammatory cytokine levels were not affected by the administration of ARA or DHA. These results suggest that long-term ARA administration has an inhibitory effect on the tumor cytotoxicity of NK cells in rat spleen lymphocytes owing to the enhanced synthesis of PGE2 and PGD2 from ARA because of the elevated plasma ARA levels in young rats.