Article Text

Download PDFPDF
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×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.

Conclusion: 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.

  • CAIA, anticollagen II antibody induced arthritis
  • CFA, complete Freund’s adjuvant
  • CIA, collagen induced arthritis
  • CII, collagen II
  • DMARDs, disease modifying antirheumatic drugs
  • EAE, experimental autoimmune encephalomyelitis
  • IP, intraperitoneal(ly)
  • MS, multiple sclerosis
  • MTX, methotrexate
  • PBS, phosphate buffered saline
  • PIA, Pristane induced arthritis
  • RA, rheumatoid arthritis
  • TNFα, tumour necrosis factor α
  • collagen induced arthritis
  • fibroblast induced arthritis
  • experimental allergic encephalomyelitis
  • methotrexate
  • Pristane

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.