Methotrexate: Mechanism of Action in Rheumatoid Arthritis

Semin Arthritis Rheum. 1990 Dec;20(3):190-200. doi: 10.1016/0049-0172(90)90060-s.


Most studies of immune function in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) show only marginal effects on humoral or cellular immune responses. These include measurements of lymphocyte subsets, proliferative responses to mitogens, immunoglobulin production, rheumatoid factor and immune complexes. The mechanism of action of MTX in RA might be more antiinflammatory than immunosuppressive. This is supported by the rapid clinical response to drug treatment and by data from in vitro and animal studies. The inhibition of interleukin-1 (IL-1) activity or other inflammatory cytokines by MTX may play an important role in the antiinflammatory effect of MTX. MTX effects in RA are not fully understood and further studies are needed to clarify its mechanism of action. MTX has crucial effects on the cascade of events initiated by some cytokines (IL-1, IL-6, tumor necrosis factor), which plays a major role in RA and other inflammatory diseases.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antibody Formation / drug effects
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / metabolism
  • Cell Division / drug effects
  • Collagen / metabolism
  • Cytokines / metabolism
  • Endopeptidases / metabolism
  • Folic Acid / metabolism
  • Humans
  • Immunity, Cellular / drug effects
  • Methotrexate / therapeutic use*
  • Monocytes / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Collagen
  • Folic Acid
  • Endopeptidases
  • Methotrexate