Cell contact interactions in rheumatology, The Kennedy Institute for Rheumatology, London, UK, 1-2 June 2000.
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several proinflammatory loops involv9ing tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-alpha and IL-1beta in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1alpha (SDF-1alpha) which enhances the expression of CD40L in T cells, which stimulates SDF-1alpha production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1beta and TNF-alpha also induce IL-15 in fibroblast like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1beta and TNF-alpha production in monocyte-macrophages. This underlies the importance of TNF-alpha and IL-1beta in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-beta) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-beta, IL-15 antagonist, or SDF-1alpha antagonist, might be of interest in RA therapy.
Burger
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Clinical Immunology Unit, Division of Immunology and Allergy, University Hospital, Geneva, Switzerland. danielle.burger@hcuge.ch
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*