Background:

Methotrexate, a folate antagonist, is a potent anti-inflammatory agent when used weekly in low concentrations, the anti-phlogistic action of which is due to increased adenosine release at inflamed sites. Studies have demonstrated that methotrexate polyglutamates are active inhibitors of several enzymatic reactions, including dihydrofolate reductase. On consideration of biochemical pharmacology of methotrexate of methotrexate, it is taken up by cells and tissues and converted to methotrexate–polyglutamates, long-lived derivatives that retain biochemical and biologic activity within the cell. There is evidence that methotrexate does not act in rheumatoid arthritis (RA) simply as a cytotoxic agent for the cells responsible for the inflammation.

Reference

[1].Bruce N. Cronstein, Dwight Naime, Edward Ostad. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. Journal of Clinical Investigation. 1993 December; 92(6): 2675–2682.
[2].Bruce N. Cronstein. The mechanism of action of methotrexate. Rheumatic Disease Clinics of North America Volume 23, Issue 4, 1 November 1997, Pages 739–755.