Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis
Autor: | Ewa M. Paleolog, P T Chapman, M Feldmann, M J Elliott, R V McCloskey, Peter C. Taylor, Ravinder Nath Maini, A. M. Peters |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Granulocyte migration
Chemokine biology business.industry medicine.medical_treatment Immunology medicine.anatomical_structure Cytokine Rheumatology biology.protein medicine Immunology and Allergy Synovial fluid Pharmacology (medical) Tumor necrosis factor alpha Interleukin 8 Synovial membrane business Macrophage inflammatory protein |
Popis: | 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 joints. |
Databáze: | OpenAIRE |
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