Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis.
This review presents recent data supporting the methotrexate (MTX) mechanisms of action, which are likely to account for its anti-proliferative and immunosuppressive effects in rheumatoid arthritis (RA). The effects of MTX in vivo may be mediated by reducing cell proliferation, increasing the rate of apoptosis of T cells, increasing endogenous adenosine release, altering the expression of cellular adhesion molecules, influencing production of cytokines, humoral responses and bone formation. Several reports indicate that the effects of MTX are influenced by genetic variants, specific dynamic processes and micro-environmental elements such as nucleotide deprivation or glutathione levels. The challenge for the future will be linking biological and genetic markers relevant to the response to MTX in RA.
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
J A M
JA
Wessels
T W J
TW
Huizinga
H-J
HJ
Guchelaar
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D016207:Cytokines; D017382:Reactive Oxygen Species; D005492:Folic Acid; D000241:Adenosine; D008727:Methotrexate