Abstract
Methotrexate was developed in 1948 for neoplastic diseases such as leukemia. Recently low dose methotrexate has been widely used on nonneoplastic diseases such as rheumatoid arthritis. Clinical studies have shown that the administration of low dose methotrexate (5.0-7.5 mg/person, once a week) to patients with rheumatoid arthritis causes clinical improvement. Then low dose methotrexate (0.1-0.3 mg/head, 3 times a week) was given to animal experimental models for arthritis and evaluated its efficacy histopathologically and immunologically.Spontaneous polyarthritis in MRL/Mp-lpr/lpr (MRL/l) mice and type II collagen induced arthritis (CIA) in DBA/1 J mice were studied. Two different studies were carried out in the CIA experiment. In one experiment, Freund's complete adjuvant (FCA) was given in both immunization and elicitation procedures. In the next experiment, FCA was used in immunization, and Freund's incomplete adjuvant (FIA) was applied in the elicitation period.The experiments revealed evidences that methotrexate had appreciable effects on the spontaneous polyarthritis in MRL/l mice and FCA/FCA CIA in DBA/1 J mice. But it provided marked improvement on FCA/FIA CIA in DBA/1J mice in a dose dependent manner. Proliferative inflammatory articular lesion was suppressed and bone remodelling effect was observed under microscope. The bone remodelling effect indicates suppression of both bone absorpsion and new bone formation.FACStar analysis provided data that methotrexate did not change number of immune responsive cells in the spleen of MRL/l mice.The folic acid antagonist methotrexate blocks the activity of dihydrofolate reductase. The mouse enzyme has decreased rate of folate reduction. That is the reason why methotrexate had appreciable effect in mice. Scientists have to pay much attention to the metabolism of the animals, and to do effort to develop newer experimental animal models.
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