Synergism of methotrexate with imuran and with 5-fluorouracil and their effects on hemolysin plaque-forming cell production in the mouse.

The present study has provided evidence that the ad ministration of methotrexate (MTX) and 5-fluorouracil (5-FU) together in the proper regimen results in a synergistic suppression of 19 S hemolysin plaque-forming cell production. A similar effect was demonstrated when a com bination of Imuran (IM) and MTX was used although the degree of potentiation was not as great. The administration of MTX (1 mg/kg) 15 min prior to the administration of 5-FU (50 mg/kg) resulted in very strong (90%) inhibition of hemolysin plaque-forming cell production in C3HeB/FeJ female mice. If the direction of administration was re versed, that is 5-FU before MTX, particularly when the interval between the two was less than 6 hr, little inhibition was observed (12 to 30%). The interaction of IM and MTX was synergistic if IM was given prior to MTX but additive if IM was given after MTX. These types of drug-drug interactions may prove useful in the control of immune re actions, in particular, the production of serum-blocking factor. Such a potent inhibitor of humoral antibody produc tion may provide a beneficial shift of tumor immunity in favor of the host.