Effects of 5-fluorouracil on human mitogen-activated peripheral blood lymphocytes from healthy individuals

Background: The effect of 5-fluorouracil (5-FU) on activated lymphocytes was explored. Materials and Methods: The in vitro effects of 5-FU on DNA synthesis in mitogen-activated lymphocytes from healthy volunteers were compared to those of the antimetabolites doxorubicin, cyclophosphamide and 6-mercaptopurine. These effects were assessed by alterations in the phenotypic profile and the percentage of cells in various phases of the cell cycle, as well as by the secretion of T helper (Th)1 and Th2 cytokines (ELISA). Results: Unlike 5-FU, the other antimetabolites failed to augment DNA synthesis in activated lymphocytes. The effect of 5-FU correlated with an increase in the percentage of cells in the S-phase and caused an increased in CD4⁺ cells, a decrease in CD56⁺ cells and a shift of the cytokine secretion pattern from Th2 to Th1. Conclusion: 5-FU exhibited a unique effect on DNA synthesis in activated lymphocytes which was accompanied by selective effects on various lymphocyte subpopulations.