Adenosine mediates the antiinflammatory effects of methotrexate as well as its toxicities

Methotrexate remains the mainstay of therapy for rheumatoid arthritis yet its mechanism of action remains unclear. Recent work from our laboratory indicates that methotrexate promotes increased adenosine release from cells and tissues and that the anti-inflammatory actions of methotrexate are mediated by adenosine, acting at its receptors on inflammatory and other cells. Similarly, evidence from our laboratory suggests that such toxicities as methotrexate-accelerated nodulosis and methotrexate-induced hepatic fibrosis are mediated by adenosine acting at its receptors.