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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.

Original publication

DOI

10.1002/1529-0131(200001)43:1<38::aid-anr6>3.0.co;2-l

Type

Journal article

Journal

Arthritis and rheumatism

Publication Date

01/2000

Volume

43

Pages

38 - 47

Addresses

Kennedy Institute of Rheumatology, London, UK.

Keywords

Joints, Synovial Membrane, Synovial Fluid, B-Lymphocytes, Leukocytes, Neutrophils, T-Lymphocytes, Humans, Arthritis, Rheumatoid, Indium Radioisotopes, Growth Substances, Intercellular Signaling Peptides and Proteins, Tumor Necrosis Factor-alpha, Immunoglobulins, Intravenous, Cell Adhesion Molecules, Lectins, Chemokines, Chemokines, CXC, Interleukin-8, Macrophage Inflammatory Proteins, Antigens, CD, Antigens, CD3, Antigens, Differentiation, B-Lymphocyte, Chemotactic Factors, Antibodies, Monoclonal, Cell Movement, Aged, Middle Aged, Female, Male, Antigens, CD22, Chemokine CCL2, Chemokine CCL5, Chemokine CXCL1, Chemokine CCL3, Chemokine CCL4