Methotrexate treatment suppresses local cytokine and chemokine production in rat adjuvant arthritis.
Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by current treatments. Methotrexate (M7X), a small molecular weight compound, has been the gold standard in the treatment of RA. It has several anti-inflammatory activities, but their contribution to its antiarthritic effects has not yet been established. We conducted a rat adjuvant arthritis study, in which we investigated the effect of MTX on local cytokine and chemokine production in arthritic paws. Our data demonstrate that MTX was able to significantly suppress cytokine and chemokine release in the inflamed joints in a dose-dependent fashion, accompanied by amelioration of the disease as indicated by reduced paw swelling and arthritic scores. These findings prompt further studies to clarify whether these suppressive effects of MTX on local cytokine and chemokine release are direct or whether they are a result of other preceding anti-inflammatory activities of the compound.
Barsig
J
J
Inflammation Pharmacology, Altana Pharma AG, Konstanz, Germany. johannes.barsig@altanapharma.com
Yam
G
G
Lehner
M D
MD
Beume
R
R
D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew
D018501:Antirheumatic Agents; D018925:Chemokines; D016207:Cytokines; D008727:Methotrexate