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 tumo r immunity of the liver, natural killer (NK) cell activity was estimat ed in the rat liver. In an in vitro study, NK-enriched mononuclear cel ls 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 incub ation. In an in vivo study, the continuous intraportal administration of chemotherapeutic (5-FU/MMC) and chemoimmunotherapeutic (5-FU/MMC/le ntinan) agents was carried out in rats for 5 days, and NK-enriched mon onuclear cells were then collected from the liver for the measurement of NK activity. Neither 5-FU alone nor the 5-FU/MMC combination affect ed NK activity in vitro. In the in vivo study, however, the 5-FU/MMC c ombination significantly decreased NK activity, and the addition of le ntinan recovered the activity to the control level. It can thus be con cluded that the intraportal administration of chemotherapeutic agents reduces NK activity in the liver and the addition of an immunostimulat or to such agents prevents this reduction. (C) 1995 Wiley-Liss. Inc.