Interactions of 2',2'-diflurodeoxycytidine (gemcitabine) with tumor necrosis factor alpha or its mutein VI in murine leukemias L1210 and P388.

The interactions of 2',2'-difluorodeoxycytidine (gemcitabine) with tumor necrosis factor alpha (TNF-alpha) or its mutein VI on the survival time of mice bearing L1210 and P388 leukemia was investigated. Four hundred eighty male CD2F1 mice were used in the experiments. They were given gemcitabine (20 mg/kg) on days 1, 4, 7 and 10 after i.p. inoculation with leukemic cells (day 0). Cytokines were administered i.p. at a dose of 250 microg/kg as daily injections for 8 days or at a dose of 400 microg/kg given 2, 4, 6 and 8 days after day 0. Drugs were administered alone and in combination. Our study indicates that TNF-alpha and its mutein VI decrease the antileukemic effect of gemcitabine on murine leukemias L1210 and P388.