Inhibition of human granulocyte function by methotrexate.
Patients receiving cytotoxic drugs are at an increased risk of bacterial infection. Drug-induced leukopenia may be responsible for depression of host defenses; however, 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, we investigated the effects of this drug on antibacterial and metabolic functions of normal polymorphonuclear leukocytes in vitro. Phagocytosis, quantitative protein iodination, and staphylococcal killing of normal polymorphonuclear leukocytes were found to decrease 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 methotrexate. The concentrations of methotrexate that produced these impairments are readily achieved in vivo and may alter antibacterial defenses in patients receiving this therapy.
D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005492:Folic Acid / Q000494:pharmacology; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007455:Iodine / Q000378:metabolism; D002955:Leucovorin / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects*; D008727:Methotrexate / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*
D005492:Folic Acid; D007455:Iodine; D002955:Leucovorin; D008727:Methotrexate