© 1992 British Society for Rheumatology
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TNF
—A PIVOTAL ROLE IN RHEUMATOID ARTHRITIS?
The Charing Cross Sunley Research Centre Lurgan Avenue, Hammersmith W6 8LW
*The Kennedy Institute of Rheumatology Bute Gardens, Hammersmith W6 7DW
Correspondence to:
Correspondence to Dr F. M. Brennan
This review seeks to describe data which support the concept that TNF
has a pivotal role in the pathogenesis of RA. There is now compelling evidence from in vitro studies and in animal models that this is the case. The in vitro studies suggest that the direct pathogenic effects of TNF are amplified by its potential to act as a potent paracrine molecule, by inducing other pro-inflammatory molecules such as IL-1, and GM-CSF. It has yet to be established whether similar paracine effects of TNF- are observed in the collagen type II mouse, or in human TNF transgenic mice, where (as discussed in this review), TNF undoubtedly has a pathogenic involvement. During the ongoing inflammation in RA, TNF (and other mediators?) induce the production of soluble TNF-R which can act as natural inhibitors. This process is, however, inadequate within the inflamed synovium, due to the fact that cytokine interactions are very local, through autocrine and paracrine mechanisms. In this environment there is a continuous competition between the interactions of surface or soluble receptor with TNF. It may well be that soluble TNF-Rs play a more important role in the periphery where they act as an essential clearance mechanism for the ligand. If, as the available data suggest, TNF does indeed have a pivotal role in the pathogenesis of RA, this needs to be verified by demonstrating that removal of TNF locally in the synovial joint of RA patients has a significant effect on clinical parameters of disease, and the progression of the disease process itself.
KEY WORDS: Tumour necrosis factor , Rheumatoid arthritis, Tumour necrosis factor receptor, Soluble TNF receptor, Interleukin 1
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