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 polyarthritis in MRL/Mp-Ipr/Ipr (MRL/I) mice and type II collagen-induced arthritis (CIA) in DBA/1J mice were studied. In one experiment, complete Freund's adjuvant (CFA) was given in both the immunization and booster procedures. In the next experiment, CFA was used for immunization and incomplete Freund's adjuvant (IFA) was given in the booster period. The experiments revealed that methotrexate had appreciable effects on arthritis 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 mice in a dose-dependent manner. Proliferative inflammatory articular lesions were suppressed and a bone-remodelling effect was observed under a microscope. The bone-remodelling effect indicates both suppression of bone absorption and new bone formation. FACStar analysis provided data that methotrexate does not change the number of immune responsive cells in the spleen of BALB/c mice. Methotrexate is a folic acid antagonist which blocks the activity of dihydrofolate reductase. This mouse enzyme has a decreased rate of folate reduction. This is why methotrexate has an appreciable effect on mice.