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The Role of TNF-alpha in the Pathogenesis of Inflammation and Joint Destruction in Rheumatoid Arthritis (RA): A Study Using a Human RA/SCID Mouse Chimera

The Role of TNF-alpha in the Pathogenesis of Inflammation and Joint Destruction in Rheumatoid Arthritis (RA): A Study Using a Human RA/SCID Mouse Chimera

H Matsuno, K Yudoh, R Katayama, F Nakazawa, M Uzuki, T Sawai, T Yonezawa, Y Saeki, G S Panayi, C Pitzalis, T Kimura

Rheumatology (Oxford). 2002 Mar;41(3):329-37.

PMID: 11934972

Abstract:

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 microg/mouse) and histological changes were examined 4 weeks after the initial treatment. Secondly, a total of 100 microg of recombinant TNF-alpha or IL-6 (0.6 microg/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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412912	Monoclonal Anti-TNF antibody produced in mouse			Price

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