Background
Tumor necrosis factor alpha (TNF-α) is found at high concentrations in the rheumatoid joint and induces upregulation of synovial fibroblast IL-15, a cytokine known to induce fibroblast proliferation through an autocrine loop. The mechanism of action of low-dose oral methotrexate (MTX) is not well understood. By inhibiting AICAR transformylase, MTX has been described to induce the extra-cellular release of the potent anti-inflammatory autacoid adenosine.