Influence of low doses of methotrexate on superoxide anion production by polymorphonuclear leukocytes from patients with rheumatoid arthritis

J Rheumatol. 1995 Apr;22(4):633-8.


Objective: The mechanism of methotrexate (MTX) action in rheumatoid arthritis (RA) is unclear. We assessed the influence of MTX on neutrophil superoxide production evaluated by ferricytochrome c reduction.

Methods: Neutrophils were collected from MTX treated patients with RA (MTX-RA), patients with RA without medication (RA) and healthy donors, cocultured with MTX or MTX-RA serum.

Results: Polymorphonuclear leukocytes (PMN) from MTX-RA showed decreased superoxide production when compared with cells collected from patients with RA and controls. Control PMN superoxide production was inhibited (36%) by MTX-RA serum incubation. This reduction was accompanied by clinical improvement. MTX had no activity in the in vitro assays.

Conclusion: MTX treatment may interfere with neutrophil superoxide production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anions / metabolism
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Blood Physiological Phenomena
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Methotrexate / pharmacology*
  • Middle Aged
  • Neutrophils / metabolism*
  • Superoxides / metabolism*


  • Anions
  • Superoxides
  • Methotrexate