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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.

Type

Journal article

Journal

Clin Exp Rheumatol

Publication Date

03/1993

Volume

11 Suppl 8

Pages

S173 - S175

Keywords

Animals, Antibodies, Monoclonal, Arthritis, Rheumatoid, Cytokines, Humans, Joints, Mice, Receptors, Cell Surface, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha