IMMUNOTOXICITY OF POLYUNSATURATED FATTY-ACIDS IN SERUM-FREE MEDIUM

To test the effect of purified polyunsaturated fatty acids on immune c ells in vitro, human peripheral blood mononuclear cells and murine spl een cells were incubated in Opti-MEM medium without serum or even albu min and with 2-mercapto-ethanol, insulin, transferrin and selenium as supplements, The human cells were stimulated with phytohemagglutinin a nd the murine cells were stimulated with Concanavalin A or lipopolysac charide. Both human and murine cells were stimulated with recombinant human interleukin-2 to generate lymphokine activated killer cells. Lin oleic and linolenic acids inhibited all of the immune responses tested , whereas docosahexaenoic and eicosapentaenoic acids did not. Similar effects were observed with cultured B16.F10 murine melanoma cells. Mix tures of linoleic and docosahexaenoic or eicosapentaenoic acids also i nhibited the mitogenic response to phytohemagglutinin. Inhibition of l ipid mediator production by indomethacin, quercetin, rutin, or nordihy droguariaretic acid, and addition of vitamins C and E with anti-oxidan t activity failed to reverse the effects of linoleic acid. Thus, linol eic and linolenic acids appear to directly inhibit immune and tumor ce lls, at least under these conditions.