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The analysis of suppression of cytokines in rheumatoid synovial tissue and fluid pioneered the studies of human cytokines in diseased tissue due to the relative ease of staining samples, even at the height of the inflammatory process. These studies led to the study of synovial cytokine regulation, and the identification of TNF as a therapeutic target, which has been amply validated in clinical trials and now routine therapy. The next key question was how is TNF disregulated in synovium. Are there differences between the mechanisms of synovial TNF production compared to the production of protective TNF during an immune response? Are there differences between the induction of the pro-inflammatory TNF and the anti inflammatory IL-10? The analysis of the interaction of the two most abundant synovial cells, T lymphocytes and macrophages has provided interesting clues to new therapeutic approaches based on disrupting T-macrophage interaction.

Type

Journal article

Journal

Current topics in microbiology and immunology

Publication Date

01/2006

Volume

305

Pages

177 - 194

Addresses

Imperial College of Science, Technology and Medicine, Kennedy Institute of Rheumatology Division, Faculty of Medicine, London, UK. f.brennan@imperial.ac.uk

Keywords

T-Lymphocytes, Monocytes, Macrophages, Animals, Humans, Arthritis, Rheumatoid, Cytokines, Lymphocyte Activation, Cell Communication, Signal Transduction, Cell Lineage