In Vitro Modulation of Interleukin-2-mediated Human Peripheral Mononuclear Cell Proliferation and Antitumor Cytotoxicity by 5-Fluorouracil

Abstract

Background: Studies on cancer patients undergoing chemotherapy have shown inhibitory effects of anticancer drugs on certain immune activities. Materials and Methods: The in vitro effect of 5-(FU) fluorouracil was studied on both lymphocyte proliferation and natural killer (NK) cell antitumor cytotoxicity following incubation of peripheral mononuclear cells (PBMCs) from healthy donors with interleukin (IL)-2, phytohemagglutinin A (PHA) and pokeweed mitogen (PWM). Results: Activation of PBMCs with IL-2, PHA and PWM in the presence of 250 and 2500 μM of 5-FU caused a marked decrease in both the induction of activated natural killer (ANK) cell cytotoxic activity and DNA synthesis, while 2.5 μM increased DNA synthesis by 195%, 58% and 222% for IL-2, PHA and PWM, respectively, more than cells cultured without the drug. No effect of 5-FU was noted on mature ANK cells. Conclusion: 5-FU exhibits diverse effects on lymphocyte proliferation and on the generation of ANK antitumor cytotoxic activity.