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Tumour necrosis factor α as a therapeutic target for immune-mediated inflammatory diseases

The Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College London, 1 Aspenlea Road, London W68LH, UK.
Current Opinion in Biotechnology (Impact Factor: 8.04). 01/2005; 15(6):557-63. DOI: 10.1016/j.copbio.2004.09.005
Source: PubMed

ABSTRACT Preclinical studies have identified and validated tumour necrosis factor alpha (TNFalpha) as a key disease molecule and therapeutic target for immunotherapeutic intervention in many immune-mediated inflammatory diseases. Clinical indications include rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriasis. Recent clinical findings indicate that many chronic inflammatory disorders share certain pathogenic pathways, whereas others are limited to particular disease phenotypes. Better understanding of these pathogenic pathways will inform the development of new therapeutic approaches leading to more complete and sustained disease remissions.

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    • "As DC migration is essential during both steady-state conditions in the absence of inflammation, as well as during inflammation, DCs were co-cultured either with resting fibroblasts or with fibroblasts stimulated with TNFa and IL-1b to mimic a proinflammatory tissue microenvironment. TNFa and IL-1b were chosen as stimuli, as they are highly expressed during cutaneous inflammation (Taylor et al., 2004; Aggarwal et al., 2006). Resting fibroblasts did not significantly enhance the secretion of MMP-9 from immature DCs. "
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    • "TNFa was identified as a key pathogenic molecule in rheumatoid arthritis as well as in Crohn's disease, ankylosing spondylitis and psoriasis. Recent clinical research using biological therapies for targeting TNFa demonstrates the important common role of TNFa in molecular pathways across a range of chronic immunomediated disease phenotypes [34]. Other major cytokines identified at inflammatory cites include IL-6, IL-1h, interferon-g and transforming growth factor h [35]. "
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