Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis

Arthritis Rheum. 2000 Jan;43(1):38-47. doi: 10.1002/1529-0131(200001)43:1<38::AID-ANR6>3.0.CO;2-L.

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 joints.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD / analysis
  • Antigens, Differentiation, B-Lymphocyte / analysis
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / therapy*
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • CD3 Complex / analysis
  • Cell Adhesion Molecules*
  • Cell Movement / immunology*
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / immunology
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / blood
  • Chemokine CCL5 / immunology
  • Chemokine CXCL1
  • Chemokines / blood*
  • Chemokines / immunology
  • Chemokines, CXC*
  • Chemotactic Factors / blood
  • Chemotactic Factors / immunology
  • Female
  • Growth Substances / blood
  • Growth Substances / immunology
  • Humans
  • Immunoglobulins, Intravenous
  • Indium Radioisotopes
  • Intercellular Signaling Peptides and Proteins*
  • Interleukin-8 / blood
  • Interleukin-8 / immunology
  • Joints / cytology
  • Joints / immunology
  • Joints / metabolism
  • Lectins*
  • Leukocytes / chemistry
  • Leukocytes / cytology*
  • Leukocytes / immunology
  • Macrophage Inflammatory Proteins / blood
  • Macrophage Inflammatory Proteins / immunology
  • Male
  • Middle Aged
  • Neutrophils / chemistry
  • Neutrophils / cytology
  • Neutrophils / immunology
  • Radionuclide Imaging
  • Sialic Acid Binding Ig-like Lectin 2
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • CD22 protein, human
  • CD3 Complex
  • CXCL1 protein, human
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Growth Substances
  • Immunoglobulins, Intravenous
  • Indium Radioisotopes
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • Lectins
  • Macrophage Inflammatory Proteins
  • Sialic Acid Binding Ig-like Lectin 2
  • Tumor Necrosis Factor-alpha