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Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis

Lange, F; Bajtner, Estelle LU ; Rintisch, Carola LU ; Nandakumar, KS; Sack, U and Holmdahl, Rikard LU (2005) In Annals of the Rheumatic Diseases 64(4). p.599-605
Abstract
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. critically dependent on T cell activation (CIA, PIA, and EAE) were Results: All models known to be... (More)
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. critically dependent on T cell activation (CIA, PIA, and EAE) were Results: All models known to be 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 11 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
64
issue
4
pages
599 - 605
publisher
British Medical Association
external identifiers
  • pmid:15345503
  • wos:000227950600016
  • scopus:16344390586
ISSN
1468-2060
DOI
10.1136/ard.2004.026120
language
English
LU publication?
yes
id
c87bee8d-639f-40ad-bd85-2b445a4781ec (old id 247250)
date added to LUP
2007-08-17 17:15:15
date last changed
2017-11-12 03:56:00
@article{c87bee8d-639f-40ad-bd85-2b445a4781ec,
  abstract     = {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. critically dependent on T cell activation (CIA, PIA, and EAE) were Results: All models known to be 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 11 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.},
  author       = {Lange, F and Bajtner, Estelle and Rintisch, Carola and Nandakumar, KS and Sack, U and Holmdahl, Rikard},
  issn         = {1468-2060},
  language     = {eng},
  number       = {4},
  pages        = {599--605},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Methotrexate ameliorates T cell dependent autoimmune arthritis and encephalomyelitis but not antibody induced or fibroblast induced arthritis},
  url          = {http://dx.doi.org/10.1136/ard.2004.026120},
  volume       = {64},
  year         = {2005},
}