PMID- 10643698 OWN - NLM STAT- MEDLINE DCOM- 20000203 LR - 20220227 IS - 0004-3591 (Print) IS - 0004-3591 (Linking) VI - 43 IP - 1 DP - 2000 Jan TI - Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. PG - 38-47 AB - 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. FAU - Taylor, P C AU - Taylor PC AD - Kennedy Institute of Rheumatology, London, UK. FAU - Peters, A M AU - Peters AM FAU - Paleolog, E AU - Paleolog E FAU - Chapman, P T AU - Chapman PT FAU - Elliott, M J AU - Elliott MJ FAU - McCloskey, R AU - McCloskey R FAU - Feldmann, M AU - Feldmann M FAU - Maini, R N AU - Maini RN LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (CD22 protein, human) RN - 0 (CD3 Complex) RN - 0 (CXCL1 protein, human) RN - 0 (Cell Adhesion Molecules) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL3) RN - 0 (Chemokine CCL4) RN - 0 (Chemokine CCL5) RN - 0 (Chemokine CXCL1) RN - 0 (Chemokines) RN - 0 (Chemokines, CXC) RN - 0 (Chemotactic Factors) RN - 0 (Growth Substances) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Indium Radioisotopes) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Interleukin-8) RN - 0 (Lectins) RN - 0 (Macrophage Inflammatory Proteins) RN - 0 (Sialic Acid Binding Ig-like Lectin 2) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM CIN - Arthritis Rheum. 2001 Jan;44(1):245-6. PMID: 11212171 CIN - Arthritis Rheum. 2001 Dec;44(12):2937-9. PMID: 11762957 MH - Aged MH - Antibodies, Monoclonal/therapeutic use MH - Antigens, CD/analysis MH - Antigens, Differentiation, B-Lymphocyte/analysis MH - Arthritis, Rheumatoid/diagnostic imaging/*immunology/*therapy MH - B-Lymphocytes/chemistry/cytology/immunology MH - CD3 Complex/analysis MH - *Cell Adhesion Molecules MH - Cell Movement/*immunology MH - Chemokine CCL2/blood/immunology MH - Chemokine CCL3 MH - Chemokine CCL4 MH - Chemokine CCL5/blood/immunology MH - Chemokine CXCL1 MH - Chemokines/*blood/immunology MH - *Chemokines, CXC MH - Chemotactic Factors/blood/immunology MH - Female MH - Growth Substances/blood/immunology MH - Humans MH - Immunoglobulins, Intravenous MH - Indium Radioisotopes MH - *Intercellular Signaling Peptides and Proteins MH - Interleukin-8/blood/immunology MH - Joints/cytology/immunology/metabolism MH - *Lectins MH - Leukocytes/chemistry/*cytology/immunology MH - Macrophage Inflammatory Proteins/blood/immunology MH - Male MH - Middle Aged MH - Neutrophils/chemistry/cytology/immunology MH - Radionuclide Imaging MH - Sialic Acid Binding Ig-like Lectin 2 MH - Synovial Fluid/cytology/immunology/metabolism MH - Synovial Membrane/cytology/immunology/metabolism MH - T-Lymphocytes/chemistry/cytology/immunology MH - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/immunology EDAT- 2000/01/22 00:00 MHDA- 2000/01/22 00:01 CRDT- 2000/01/22 00:00 PHST- 2000/01/22 00:00 [pubmed] PHST- 2000/01/22 00:01 [medline] PHST- 2000/01/22 00:00 [entrez] AID - 10.1002/1529-0131(200001)43:1<38::AID-ANR6>3.0.CO;2-L [doi] PST - ppublish SO - Arthritis Rheum. 2000 Jan;43(1):38-47. doi: 10.1002/1529-0131(200001)43:1<38::AID-ANR6>3.0.CO;2-L.