EFFECTS OF METHOTREXATE ON SPONTANEOUS ARTHRITIS IN MRL I MICE AND TYPE-II COLLAGEN-INDUCED ARTHRITIS IN DBA/1J MICE/

The effect of low-dose methotrexate was studied in animal experimental models for arthritis to evaluate its efficacy. Spontaneous polyarthri tis in MRL/Mp-Ipr/Ipr (MRL/I) mice and type II collagen-induced arthri tis (CIA) in DBA/1J mice were studied. In one experiment, complete Fre und's adjuvant (CFA) was given in both the immunization and booster pr ocedures. In the next experiment, CFA was used for immunization and in complete Freund's adjuvant (IFA) was given in the booster period. The experiments revealed that methotrexate had appreciable effects on arth ritis in MRL/I mice and on CIA in the CFA/CFA group of DBA/1J mice. It provided marked improvement of CIA in the CFA/IFA group of DBA/1J mic e in a dose-dependent manner. Proliferative inflammatory articular les ions were suppressed and a bone-remodelling effect was observed under a microscope. The bone-remodelling effect indicates both suppression o f bone absorption and new bone formation. FACStar analysis provided da ta that methotrexate does not change the number of immune responsive c ells in the spleen of BALB/c mice. Methotrexate is a folic acid antago nist which blocks the activity of dihydrofolate reductase. This mouse enzyme has a decreased rate of folate reduction. This is why methotrex ate has an appreciable effect on mice.