Methotrexate: Mechanism of action in rheumatoid arthritis

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Abstract

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 play a major role in RA and other inflammatory diseases.

References (55)

  • S Koizumi et al.

    Formation of methotrexate polyglutamates in purified myeloid precursor cells from normal human bone marrow

    J Clin Invest

    (1985)
  • SC Morgan et al.

    Folate status of RA patients receiving long term low dose MTX therapy

    Arthritis Rheum

    (1987)
  • M Tishler et al.

    The effect of leucovorin on methotrexate therapy in rheumatoid arthritis

    Arthritis Rheum

    (1988)
  • ME Weinblatt et al.

    Efficacy of low-dose methotrexate in rheumatoid arthritis

    N Engl J Med

    (1985)
  • ME Weinblatt et al.

    Long term prospective study of methotrexate in rheumatoid arthritis

    Arthritis Rheum

    (1988)
  • PA Andersen et al.

    Weekly pulse methotrexate in rheumatoid arthritis

    Ann Intern Med

    (1985)
  • NJ Olsen et al.

    Immunologic studies of rheumatoid arthritis patients treated with methotrexate

    Arthritis Rheum

    (1987)
  • NJ Olsen et al.

    Antiproliferative effects of methotrexate on peripheral blood mononuclear cells

    Arthritis Rheum

    (1989)
  • AMW O'Meara et al.

    The effect of methotrexate on in vitro immunoglobulin production

    J Immunopharmacol

    (1985)
  • GJ Rosenthal et al.

    Suppression of B cell function by methotrexate and trimetrexate. Evidence of inhibition of purine biosynthesis as well as a major mechanism of action

    J Immunol

    (1988)
  • GR Burmeister et al.

    Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis

    Scand J Immunol

    (1978)
  • AS Russell et al.

    The activity of natural killer cells in patients with rheumatoid arthritis: I. The effect of drugs used in vivo

    Clin Exp Rheumatol

    (1984)
  • DS Matheson et al.

    The influence of methotrexate and thymidine on the human natural killer cell function in vitro

    J Immunol

    (1983)
  • CA Johnston et al.

    Measurement of immunologic and inflammatory responses in vitro in rheumatoid arthritis patients treated with methotrexate

    J Rheumatol

    (1986)
  • DS Rosenblatt et al.

    Prolonged inhibition of DNA synthesis associated with the accumulation of methotrexate polyglutamates by cultured human cells

    Mol Pharmacol

    (1978)
  • CA Johnston et al.

    The effect of in vivo and in vitro methotrexate on lymphocyte proliferation as measured by the uptake of tritiated thymidine and tritiated guanosine

    Clin Exp Rheumatol

    (1988)
  • S Rodenhuis et al.

    Increase of dihydrofolate reductase in peripheral blood lymphocytes of rheumatoid arthritis patients treated with low-dose oral methotrexate

    Arthritis Rheum

    (1987)
  • Cited by (0)

    1

    From the Department of Rheumatology, Ichilov Hospital, Tel-Aviv University, Sackler School of Medicine, and the Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.

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