Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Williams, A. S.
Right arrow Articles by Williams, B. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williams, A. S.
Right arrow Articles by Williams, B. D.
Related Collections
Right arrow Experimental Arthritis
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Rheumatology 2001; 40: 375-383
© 2001 British Society for Rheumatology

Amelioration of rat antigen-induced arthritis by liposomally conjugated methotrexate is accompanied by down-regulation of cytokine mRNA expression

A. S. Williams, N. Topley1, S. Dojcinov2, P. J. Richards and B. D. Williams

Department of Rheumatology,
1 Department of Nephrology and
2 Department of Histopathology, University of Wales College of Medicine, Heath Park, Cardiff, UK

Objectives. We examined the temporal changes in the expression of interleukin 1ß (IL-1ß), tumour necrosis factor {alpha} (TNF-{alpha}) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV).

Methods. On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1ß and TNF-{alpha}) using semiquantitative reverse transcription–polymerase chain reaction.

Results. There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94±0.12 mm; P<0.0001) compared with rats treated with MTX (3.17±0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1ß mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7.

Conclusions. Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1ß and IL-6 inhibition.

KEY WORDS: Antigen-induced arthritis, Methotrexate, Rat, Liposomes, Gene expression.

Correspondence to: A. S. Williams, Rheumatology Research Laboratory, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.