Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis.
OBJECTIVE
To investigate the mode of action of methotrexate (MTX) in different types of models for rheumatoid arthritis (RA) and multiple sclerosis (MS).


METHODS
Models for RA and MS were selected known to have different pathogenesis--that is, fibroblast induced arthritis in SCID mice, collagen induced arthritis (CIA), anticollagen II antibody induced arthritis (CAIA), and experimental autoimmune encephalomyelitis (EAE) in (Balb/c x B10.Q)F1 and B10.Q mice, and Pristane induced arthritis in DA rats (PIA). The MTX treatment was started 1 day after the onset of disease and continued for 14 days to compare effects on the different models.


RESULTS
All models known to be critically dependent on T cell activation (CIA, PIA, and EAE) were effectively down regulated by titrated doses of MTX. In contrast, no effects were seen on fibroblast induced arthritis or CAIA. No effects were seen on the levels of anticollagen II antibodies in the CIA experiment.


CONCLUSIONS
The data show that MTX has strong ameliorative effect on both classical models of RA, like CIA and PIA, but also on a model for MS, EAE. It also suggests that MTX operates only in diseases which are preceded by, and dependent on, T cell activation. A comparison of CAIA and CIA suggested that MTX operates independently of arthritogenic antibodies. These results demonstrate that different animal models reflect the complexity of the corresponding human diseases and suggest that several models should be used for effective screening of new therapeutic agents.
Lange
F
F
Department of Clinical Immunology and Transfusion Medicine, Leipzig University, Germany.
Bajtner
E
E
Rintisch
C
C
Nandakumar
K S
KS
Sack
U
U
Holmdahl
R
R
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008727:Methotrexate / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID
D018501:Antirheumatic Agents; D001323:Autoantibodies; D024043:Collagen Type II; D007166:Immunosuppressive Agents; D008727:Methotrexate