Increased peripheral blood leukocyte cytotoxic activity in cancer patients during the continuous intravenous administration of recombinant human tumor necrosis factor

Peripheral blood leukocyte cytotoxic activity was studied in cancer patients being treated with a continuous 5-day intravenous infusion of recombinant human tumor necrosis factor (TNF) at a dose of 40 micrograms/m2/day. All of the nine patients tested experienced a marked increase in circulating leukocyte cytotoxic activity over the 5-day course of treatment. The increase in cytotoxic activity was paralleled by an overall decrease in the number of peripheral blood leukocytes. The percentage of circulating Leu 19+ natural killer cells fell in all patients, while the numbers of both Leu 4+ T cells and Leu 19+/Leu 4+ cytotoxic T cells remained constant. Our findings suggest that the intravenous administration of recombinant TNF may be accompanied by an immunoenhancement due either to an improvement in cytotoxic cell function or to alterations in the trafficking of leukocytes.