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

Objective. To verify the hypothesis that in rheumatoid ;arthritis (RA), tum or necrosis factor alpha (TNF alpha) plays a critical role in regulating le ukocyte trafficking and chemokine levels, Methods. Ten patients with longstanding RA received a single 10 mg/kg infus ion of anti-TNF alpha monoclonal antibody (cA2), The articular localization of autologous granulocytes, separated in vitro and labeled with In-111, wa s 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+ macrophag es, Synovial tissue expression of the chemokines interleukin-8 (IL-8), mono cyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, Gro alpha, and RANTES was also determined. Seru m IL-8 and MCP-1 concentrations were measured by enzyme-linked immunosorben t assay. Results, Anti-TNF alpha therapy in RA significantly reduced In-111-labeled granulocyte migration into affected joints. There was a simultaneous and si gnificant reduction in the numbers of infiltrating synovial CD3+ T cells, C D22+ B cells, and CD68+ macrophage and in the expression of IL-8 and MCP-1, with a trend toward a reduction in serum concentrations of these chemokine s, Conclusion. TNF alpha blockade reduces synovial expression of the chemokine s IL-8 and MCP-1 and diminishes inflammatory cell migration into RA joints.