THE COMBINATION 5-FLUOROURACIL LEVAMISOLE INDUCES ENHANCED RAT KUPFFER CELL-MEDIATED CYTOTOXICITY IN-VITRO AGAINST THE SYNGENEIC COLON ADENOCARCINOMA CELL-LINE CC531/

The mode of action of the combination treatment 5-fluorouracil (5-FU) and levamisole in colorectal cancer patients is unknown. It is postula ted that the beneficial effect may be explained by an immunomodulatory effect on Kupffer cell (KC) cytotoxicity. We evaluated the effect of levamisole (200 mu g/ml) and 5-FU (10 mu M) on rat KC cytotoxicity aga inst syngeneic CC531 tumor cells. Viability of KCs was unaffected by 5 -FU and/or levamisole. The combination did not enhance growth inhibiti on of CC531 compared to 5-FU alone. A significant increase in KC cytot oxicity was observed after 24-hr incubation with 5-FU/levamisole espec ially at an effector/target ratio of 10 (P < 0.05). 5-FU alone had no effect on KC cytotoxicity, while levamisole induced only a slight incr ease. Our in vitro data suggest that the additive effect of the combin ation 5-FU/levamisole on KC cytotoxicity may attribute to the benefici al effect of the adjuvant treatment in colorectal cancer patients. (C) 1995 Wiley-Liss, Inc.