TNF-alpha in rheumatoid arthritis and prospects of anti-TNF therapy

Our work has shown that TNF alpha is produced by cultured mononuclear cells from rheumatoid arthritis joints and appears to regulate the production of IL-1. Immunohistochemical examination has shown the presence of TNF alpha in the synovium, e.g. in the lining layer, some endothelial cells and most...

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Bibliographic Details
Published inClinical and experimental rheumatology Vol. 11 Suppl 8; p. S173
Main Authors Maini, R N, Brennan, F M, Williams, R, Chu, C Q, Cope, A P, Gibbons, D, Elliott, M, Feldmann, M
Format Journal Article
LanguageEnglish
Published Italy 01.03.1993
Subjects
Animals
Antibodies, Monoclonal - therapeutic use
Arthritis, Rheumatoid - etiology
Arthritis, Rheumatoid - physiopathology
Arthritis, Rheumatoid - therapy
Cytokines - physiology
Humans
Joints - physiopathology
Mice
Receptors, Cell Surface - metabolism
Receptors, Tumor Necrosis Factor
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - physiology
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Summary:Our work has shown that TNF alpha is produced by cultured mononuclear cells from rheumatoid arthritis joints and appears to regulate the production of IL-1. Immunohistochemical examination has shown the presence of TNF alpha in the synovium, e.g. in the lining layer, some endothelial cells and most importantly, in the cells in the cartilage pannus junction. TNF receptors (both p55 and p75) have a similar distribution, thereby suggesting that TNF has the potential for autocrine and paracrine activity in the joint. The concept that TNF alpha is pathogenic in inflammatory arthritis has been validated by showing that neutralizing monoclonal anti-TNF antibodies significantly attenuate collagen-induced arthritis in mice. In preliminary trials in rheumatoid patients anti-TNF appears to have an impressive effect on indices of disease activity including C-reactive production and serum amyloid-A production. TNF alpha appears to be a relevant therapeutic target in rheumatoid disease.
ISSN:0392-856X