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

Abstract

Objective To verify the hypothesis that in rheumatoid arthritis (RA), tumor necrosis factor α (TNFα) 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‐TNFα 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 1α (MIP‐1α), MIP‐1β, Groα, and RANTES was also determined. Serum IL‐8 and MCP‐1 concentrations were measured by enzyme‐linked immunosorbent assay. Results Anti‐TNFα 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 TNFα blockade reduces synovial expression of the chemokines IL‐8 and MCP‐1 and diminishes inflammatory cell migration into RA joints.