Objective. The effect of chimeric anti–tumor necrosis factor α (TNFα) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNFα 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-TNFα 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 the antiinflammatory effect of anti-TNFα 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.