The anti‐inflammatory actions of methotrexate are critically dependent upon the production of reactive oxygen species

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Abstract
The mechanism of action by which methotrexate (MTX) exerts its anti‐inflammatory and immunosuppressive effects remains unclear. The aim of this study is to investigate the hypothesis that MTX exerts these effects via the production of reactive oxygen species (ROS). Addition of MTX (100 nM–10 μM) to U937 monocytes induced a time and dose dependent increase in cytosolic peroxide [peroxide]cyt from 6–16 h. MTX also caused corresponding monocyte growth arrest, which was inhibited (Pcyt in Jurkat T cells was more rapid (4 h; PPPP0.05). However, in T‐cells, GSH levels were significantly elevated following 30 nM MTX treatment (PP−1) activated human umbilical vein endothelial cells (HUVEC; PBritish Journal of Pharmacology (2003) 138, 501–511. doi:10.1038/sj.bjp.0705054