Differential effects of 5-fluorouracil analogs on humoral and cell-mediated responses in mice: augmentation of delayed hypersensitivity response against picryl chloride by 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione (FD-1), a new anti-tumor drug.

The inhibitory effects of three fluorinated pyrimidines, i.e., 5-fluorouracil (FU), N1-(2-tetrahydrofuryl)-5-fluorouracil (ftorafur, FT), and 1,3-bis(tetrahydro-2-furanyl)-5-fluoro-2,4-pyrimidinedione (FD-1), on humoral and cell-mediated responses were compared. Both primary and secondary humoral responses against sheep red blood cells were strongly suppressed, and the suppressive activities of FD-1, FT and FU were directly proportional to the plasma level of active substance, FU. However, allogeneic skin graft rejection was not suppressed by FD-1 and FT. Furthermore, the delayed hypersensitivity response (DHR) against picryl chloride (PCl) was augmented by FD-1 but not by FT and FU if they were administrated for 3 days after PCl immunization. Spleen cells from mice immunized 7 days previously with PCl were able to suppress the occurrence of the DHR when they were transfused intravenously to normal syngeneic mice simultaneously immunized with PCl. The suppressor activity of spleen cells was due to B cells since the activity was abrogated by treatment with anti-IgG serum plus complement, but not by anti-T cell serum plus complement. However, the suppressor activity disappeared when donor mice were administrated with FD-1 and FU. It is suggested that FD-1 has a great inhibitory effect on suppressor cells than effector cells induced by PC1, and then the immunosuppressive potency of these drugs is not always reflected in the level of FU.