Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with rheumatoid arthritis

Mod Rheumatol. 2009;19(4):372-8. doi: 10.1007/s10165-009-0175-z. Epub 2009 May 21.

Abstract

This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-alpha (TNF-alpha) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-alpha were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-alpha induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-alpha may induce granzyme B and RANTES production in RA patients.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • C-Reactive Protein / analysis
  • Cells, Cultured
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / drug effects*
  • Chemokine CCL5 / blood
  • Chemokine CCL5 / drug effects
  • Etanercept
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Granzymes / blood
  • Granzymes / drug effects
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Male
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Severity of Illness Index
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antirheumatic Agents
  • CCL2 protein, human
  • CCL5 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Granzymes
  • Etanercept