Selective alteration of immunocompetence with methotrexate and 5-fluorouracil.

A drug combination comprised of methotrexate (1 mg/kg given on Day 2 of the sensitization period) followed in 1 hr by 5-fluorouracil (50 mg/kg) is capable of potentiative suppres sion of humoral antibody production without concomitant inhibition of cell-mediated immunity. Thus, this combination suppressed 19 S hemolytic antibody production in C3HeB/FeJ mice by 88% but had no inhibitory effect upon allograft rejection in A/J mice or upon contact sensitivity to oxazolone in C3HeB/FeJ mice. Treatment during the induction of hypersensitivity to methylated bovine serum albumin, a response apparently having a cell-mediated component op posed by a humoral blocking component, resulted in strong stimulation of the edematous end point in male C3HeB/FeJ mice. Stimulation of methylated bovine serum albumin-in duced hypersensitivity was also found in female mice when leucovorin was added to the regimen. This selective immunosuppressive regimen might prove beneficial in attempts to control the production of serum blocking factors.