title: Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  TNFalpha blockade reduces synovial expression of the chemokines IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints.
authors.affiliation: Kennedy Institute of Rheumatology, London, UK.
authors.forename: P C
authors.initials: PC
authors.lastname: Taylor
authors.forename: A M
authors.initials: AM
authors.lastname: Peters
authors.forename: E
authors.initials: E
authors.lastname: Paleolog
authors.forename: P T
authors.initials: PT
authors.lastname: Chapman
authors.forename: M J
authors.initials: MJ
authors.lastname: Elliott
authors.forename: R
authors.initials: R
authors.lastname: McCloskey
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: R N
authors.initials: RN
authors.lastname: Maini
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D015815:Cell Adhesion Molecules; D002465:Cell Movement / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood / Q000276:immunology; D054360:Chemokine CXCL1; D018925:Chemokines / Q000097:blood* / Q000276:immunology; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000097:blood / Q000276:immunology; D005260:Female; D006133:Growth Substances / Q000097:blood / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007205:Indium Radioisotopes; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D007596:Joints / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D037102:Lectins; D007962:Leukocytes / Q000737:chemistry / Q000166:cytology* / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D011877:Radionuclide Imaging; D051918:Sialic Acid Binding Ig-like Lectin 2; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D017252:CD3 Complex; C475829:CXCL1 protein, human; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D006133:Growth Substances; D016756:Immunoglobulins, Intravenous; D007205:Indium Radioisotopes; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D037102:Lectins; D019402:Macrophage Inflammatory Proteins; D051918:Sialic Acid Binding Ig-like Lectin 2; D014409:Tumor Necrosis Factor-alpha