Journal
RHEUMATOLOGY
Volume 41, Issue 3, Pages 329-337Publisher
OXFORD UNIV PRESS
DOI: 10.1093/rheumatology/41.3.329
Keywords
rheumatoid arthritis; SCID mouse; tumour necrosis factor; interleukin-6; pathology
Categories
Ask authors/readers for more resources
Objective. In order to elucidate which cytokine preferentially stimulates the synovium in patients with rheumatoid arthritis (RA), we investigated the roles of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) using SCID mice engrafted with human RA tissue (SCID-HuRAg). Methods. The SCID-HuRAg mice were prepared according to our previously described method. First, SCID-HuRAg mice were treated with chimeric anti-TNF-alpha. monoclonal antibody (mAb, 100 mug/mouse) and histological changes were examined 4 weeks after the initial treatment. Secondly, a total of 100 mug of recombinant TNF-alpha or IL-6 (0.6 mug/h) was administered daily to mice using an osmium pump. The histological changes and serum cytokine levels were examined 4 weeks after the initial administration. Human immunoglobulin G (IgG) was administered to mice as a control. Results. Synovial inflammatory cells were significantly decreased after the anti-TNF-alpha mAb treatment; conversely, the degree of synovial inflammation was significantly exacerbated by TNF-alpha administration. The levels of both IL-6 and TNF-alpha in sera were significantly increased by recombinant TNF-alpha administration, while TNF-alpha levels were unchanged by IL-6 administration. This suggests that TNF-alpha controls IL-6 production. Despite the profound changes in inflammation, we found no effects on bone and no articular cartilage damage was produced by TNF-alpha. Conclusion. This study provides strong evidence that TNF-alpha is a key molecule in the control of the inflammatory changes that occur in the RA synovium, In addition, TNF-alpha regulates IL-6 production, However, other inflammatory pathways independent of TNF-alpha may Contribute to the bone and cartilage damage seen in RA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available