EFFECTS OF INTRAPORTAL ADMINISTRATION OF CHEMOIMMUNOTHERAPEUTIC AGENTS ON NATURAL-KILLER-CELL ACTIVITY IN THE RAT-LIVER

To evaluate the effects of continuous intraportal chemotherapy on tumor immunity of the liver, natural killer (NK) cell activity was estimated in the rat liver. In an in vitro study, NK-enriched mononuclear cells collected from rat liver were incubated with 5-fluorouracil (5-FU) alone and with a 5-fluorouracil/mitomycin C (5-FU/MMC) combination at different concentrations. NK activity was measured after 24-hour incubation. In an in vivo study, the continuous intraportal administration of chemotherapeutic (5-FU/MMC) and chemoimmunotherapeutic (5-FU/MMC/lentinan) agents was carried out in rats for 5 days, and NK-enriched mononuclear cells were then collected from the liver for the measurement of NK activity. Neither 5-FU alone nor the 5-FU/MMC combination affected NK activity in vitro. In the in vivo study, however, the 5-FU/MMC combination significantly decreased NK activity, and the addition of lentinan recovered the activity to the control level. It can thus be concluded that the intraportal administration of chemotherapeutic agents reduces NK activity in the liver and the addition of an immunostimulator to such agents prevents this reduction. (C) 1995 Wiley-Liss. Inc.