Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis

Arthritis Rheum. 1996 Jul;39(7):1077-81. doi: 10.1002/art.1780390702.

Abstract

Objective: The effect of chimeric anti-tumor necrosis factor alpha (TNF alpha) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNF alpha therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST).

Methods: The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNF alpha MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mg/kg (n = 7).

Results: A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mg/kg of cA2 in RA patients.

Conclusion: The reduced expression of adhesion molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNF alpha therapy might be partly explained by down-regulation of cytokine-inducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / therapy*
  • Double-Blind Method
  • E-Selectin / drug effects*
  • E-Selectin / metabolism
  • Humans
  • Lymphocyte Activation / drug effects*
  • Severity of Illness Index
  • Synovial Membrane / drug effects*
  • Synovial Membrane / metabolism
  • T-Lymphocytes / drug effects*
  • Tumor Necrosis Factor-alpha / immunology*
  • Vascular Cell Adhesion Molecule-1 / drug effects*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antibodies, Monoclonal
  • E-Selectin
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1