Abstract
Tumour necrosis factor a (TNFα) was cloned and expressed as a recombinant protein in the middle 1980s and shown to be identical to “cachectin” [1, 2]. Shortly afterwards nucleic acid and monoclonal antibody probes became available that permitted analysis of the expression of TNF and its receptors in human tissue from patients and controls. The demonstration in in vitro systems that both TNF and IL-1, individually and in combination, stimulated cartilage degradation [3], bone loss [4] and production of prostaglandin E2 and collagenase [5], promoted interest in the role that these cytokines might play in rheumatoid arthritis (RA). In 1988 and 1989 experiments by Buchan et al. [6] and Brennan et al. [7] demonstrated the expression of TNFα at messenger RNA and production of TNFα protein by disaggregated cells obtained from rheumatoid synovial membranes in tissue culture. Specific antibodies were then applied to microscopic sections of synovial membrane from rheumatoid joints and showed that TNFα was present in cells in the lining layer as well as in the deeper parts of the synovium, predominantly in CD68+ cells (macrophage phenotype) but also in a minority of CD3+ T cells in perivascular areas [8]. More interestingly, it was possible to demonstrate the presence of TNFα in cells at the cartilage/pannus junction, the site of the destructive and invasive tissue that leads to the loss of cartilage and bone in rheumatoid joints [8, 9].
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Maini, R.N. (2000). The debut of anti-TNF therapy of rheumatoid arthritis in the clinic. In: Higgs, G.A., Henderson, B. (eds) Novel Cytokine Inhibitors. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8450-1_7
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DOI: https://doi.org/10.1007/978-3-0348-8450-1_7
Publisher Name: Birkhäuser, Basel
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