Reduction of leukocyte and interleukin-1 beta concentrations in the synovial fluid of rheumatoid arthritis patients treated with methotrexate

Arthritis Rheum. 1993 Sep;36(9):1244-52. doi: 10.1002/art.1780360909.


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-1 beta (IL-1 beta) 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-1 beta 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-1 beta secretion may contribute to this effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Female
  • Humans
  • Interleukin-1 / metabolism*
  • Leukocyte Count / drug effects
  • Leukocytes / cytology*
  • Lymphocyte Subsets / pathology
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Neutrophils / pathology
  • Osmolar Concentration
  • Synovial Fluid / cytology*
  • Synovial Fluid / metabolism*


  • Interleukin-1
  • Methotrexate