Journal ArticleDOI
Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis.
Peter C. Taylor,A. M. Peters,Ewa M. Paleolog,P T Chapman,M J Elliott,R V McCloskey,M Feldmann,Ravinder Nath Maini +7 more
TLDR
TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints and confirms the hypothesis that in rheumatoid arthritis, tumor necrosis factor alpha plays a critical role in regulating leukocyte trafficking and chemokine levels.Abstract:
OBJECTIVE: To verify the hypothesis that in rheumatoid arthritis (RA), tumor necrosis factor alpha (TNFalpha) plays a critical role in regulating leukocyte trafficking and chemokine levels METHODS: Ten patients with longstanding RA received a single 10 mg/kg infusion of anti-TNFalpha monoclonal antibody (cA2) The articular localization of autologous granulocytes, separated in vitro and labeled with 111In, was studied by analysis of gamma-camera images both before and 2 weeks after treatment At the same sequential time points, synovial biopsy samples were assessed for infiltrating CD3+ T cells, CD22+ B cells, and CD68+ macrophages Synovial tissue expression of the chemokines interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, Groalpha, and RANTES was also determined Serum IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosorbent assay RESULTS: Anti-TNFalpha therapy in RA significantly reduced 111In-labeled granulocyte migration into affected joints There was a simultaneous and significant reduction in the numbers of infiltrating synovial CD3+ T cells, CD22+ B cells, and CD68+ macrophages and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokines CONCLUSION: TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA jointsread more
Citations
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Journal ArticleDOI
Tumor necrosis factor signaling.
TL;DR: Some general aspects of this fascinating molecule are covered and then the molecular mechanisms of TNF signal transduction will be addressed, including the multiple facets of crosstalk between the various signalling pathways engaged by TNF.
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Tumor necrosis factor antagonist mechanisms of action: A comprehensive review
TL;DR: The biology of T NF and related family members are discussed in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases.
Journal ArticleDOI
Chemokines and disease.
Craig Gerard,Barrett J. Rollins +1 more
TL;DR: Several diseases that are associated with inappropriate activation of the chemokine network are examined, including cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease.
Journal ArticleDOI
Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned?
Marc Feldmann,Ravinder N. Maini +1 more
TL;DR: Clinical investigations in which the activity of TNF alpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNF alpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3.
Journal ArticleDOI
Tumor Necrosis Factor-α Signaling in Macrophages
TL;DR: TNFα has been shown to play a pivotal role in orchestrating the cytokine cascade in many inflammatory diseases and because of this role as a "master-regulator" of inflammatory cytokine production, it has been proposed as a therapeutic target for a number of diseases.
References
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The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
Frank C. Arnett,Steven M. Edworthy,Daniel A. Bloch,Dennis J. McShane,James F. Fries,Norman S. Cooper,L. A. Healey,Stephen R. Kaplan,Matthew H. Liang,Harvinder S. Luthra,Thomas A. Medsger,Donald M. Mitchell,David H. Neustadt,Robert S. Pinals,Jane G. Schaller,John T. Sharp,Ronald L. Wilder,Gene G. Hunder +17 more
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
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Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for the rheumatic diseases to date, and these new revised classified criteria for rheumatoid arthritis are very important as they should provide understanding of the possibly changing face of rheumatism.
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Revised criteria for the classification of rheumatoid arthritis.
TL;DR: The Bulletin on the Rheumatic Diseases has published all of the classification criteria for rheumatic diseases to date as mentioned in this paper, and these new revised classification criteria are very important as they should provide understanding of the possibly changing face of rheumatoid arthritis.
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Tissue Destruction by Neutrophils
TL;DR: With increasing frequency, the human neutrophil is being implicated as a mediator of tissue-destructive events in inflammatory diseases ranging from rheumatoid arthritis and myocardial reperfusion injury to respiratory distress syndromes, blistering skin disorders, and ulcerative colitis.
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Leukocyte-endothelial adhesion molecules.
Timothy M. Carlos,John M. Harlan +1 more
TL;DR: Investigations have progressed from the early descriptions by intravital microscopy and histology, to functional and immunologic characterization of adhesion molecules, and now to the development of genetically deficient animals and the first phase I trial of "anti-adhesion" therapy in humans.