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

ABSTRACT

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.