INHIBITION OF HUMAN GRANULOCYTE FUNCTION BY METHOTREXATE

Google Scholar
  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (3) , 650-655
Abstract
Patients receiving cytotoxic drugs are at an increased risk of bacterial infection. Drug-induced leukopenia may be responsible for depression of host defenses. There is little information concerning the qualitative effects, if any, of cytotoxic agents on granulocyte antibacterial activity. Since methotrexate is now being used in massive doses in vivo, the effects of this drug were investigated on antibacterial and metabolic functions of normal polymorphonuclear leukocytes in vitro. Phagocytosis, quantitative protein iodination and staphylococcal killing of normal polymorphonuclear leukocytes decreased with exposure to increasing concentrations of methotrexate. The effects of methotrexate on these cell functions were rapid in onset and readily reversed by washing the cells, suggesting a locus of action on the cell membrane rather than at the level of nucleic acid synthesis. Exposure of cells to similar concentrations of folic acid or folinic acid produced no impairment of bacterial phagocytosis, suggesting that the observed effects are specific for methoxtrexate. The concentrations of methotrexate that produced these impairments are readily achieved in vivo and may alter antibacterial defenses in cancer patients receiving this therapy.