How does methotrexate suppress inflammation?

Methotrexate remains the most widely used agent for the treatment of rheumatoid arthritis and other chronic inflammatory diseases. Although introduced as a chemotherapeutic agent for the treatment of malignancies, it is clear that, in the doses used, the mechanism of action in the suppression of inflammation differs from simply suppression of purine and pyrimidine metabolism, resulting in inhibition of proliferation. Here we review the proposed mechanisms of action of methotrexate.