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Ann Rheum Dis. 1999 Nov;58 Suppl 1:I32-9.

The function of tumour necrosis factor and receptors in models of multi-organ inflammation, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease.

Author information

1
Laboratory of Molecular Genetics, Hellenic Pasteur Institute, 127 Vas Sofias Avenue, Athens 115 21, Greece.

Abstract

There is now good evidence to demonstrate that aberrations in tumour necrosis factor (TNF) production in vivo may be either pathogenic or protective and several plausible mechanisms may explain these contrasting activities. According to the classic pro-inflammatory scenario, failure to regulate the production of TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses, which may consequently lead to organ specific inflammatory pathology and tissue damage. However, more cryptic functions of this molecule may be considered to play a significant part in the development of TNF mediated pathologies. Direct interference of TNF with the differentiation, proliferation or death of specific pathogenic cell targets may be an alternative mechanism for disease initiation or progression. In addition to these activities, there is now considerable evidence to suggest that TNF may also directly promote or down regulate the adaptive immune response. A more complete understanding of the temporal and spatial context of TNF/TNF receptor (TNF-R) function and of the molecular and cellular pathways leading to the development of TNF/TNF-R mediated pathologies is necessary to fully comprehend relevant mechanisms of disease induction and progression in humans. In this paper, the potential pathogenic mechanisms exerted by TNF and receptors in models of multi-organ inflammation, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease are discussed. Elucidating the nature and level of contribution of these mechanisms in chronic inflammation and autoimmunity may lead to better regulatory and therapeutic applications.

PMID:
10577971
PMCID:
PMC1766575
DOI:
10.1136/ard.58.2008.i32
[Indexed for MEDLINE]
Free PMC Article

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