Objective. To examine the effect of methotrexate (MTX) on the numbers of leukocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with active rheumatoid arthritis (RA).

Methods. Twelve patients were treated with MTX; 5 patients not taking MTX served as controls. Samples of PB and SF were collected at 0, 1, 4, and 8 weeks of the study. Disease activity was scored, and total leukocytes, neutrophils, lymphocytes, and CD4+, CD8+, DR+, and CD25+ lymphocyte subsets were analyzed in PB and SF. Interleukin-1β (IL-1β) concentrations in SF were determined.

Results. Patients treated with MTX showed significant clinical improvement. No change in PB leukocytes or lymphocyte subsets was observed in either patient group over the 8-week study period. In contrast, the number of leukocytes, the number and proportion of neutrophils, and the concentration of IL-1β in the SF of patients treated with MTX were reduced. In addition, in MTX-treated patients, there was an appreciable decrease in SF CD8+ lymphocytes, but not CD4+, DR+, or CD25+ lymphocytes.

Conclusion. These findings suggest that in RA, MTX acts, at least in part, by reducing the migration of leukocytes into the inflamed synovium. Local reduction of IL-1β secretion may contribute to this effect.