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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

New approaches to inhibiting TNF production in rheumatoid arthritis: is pathological TNF regulated in the same way as protective TNF?

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The success of antiTNF therapy of rheumatoid arthritis with infliximab (Remicade) and etanercept (enbrel) has prompted us to seek other ways of inhibiting TNF production, and to seek to determine the cellular and molecular mechanisms underlying the excess and prolonged TNF synthesis in RA.

We have studied spontaneous synovial TNF production and found it to depend on the function of synovial T cells. These T cells behave like cytokine activated T cells and not antigen activated T cells from normal individuals. This was determined by comparing the TNF response to inhibitors of PI3Kinase and of NFkB in Dayer type Tcell-macrophage cocultures, using the 3 types of T cells.

This result has important implications, at several levels. First, it ends the controversy concerning the role of T cells in late RA, they are involved, but their function is atypical. Second, it demonstrates that the synovial T cells which resemble cytokina activated T cells are a goog target for therapy. As these cells are not present in acute protective immune responses, it predicts that if it turns out that the risk of infection increases with prolonged use of TNF inhibitors, targetting TNF indirectly by this approach, for example with a monoclonal antibody, might be a safer approach.

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Feldmann, M., Foxwell, B., Maini, R. et al. New approaches to inhibiting TNF production in rheumatoid arthritis: is pathological TNF regulated in the same way as protective TNF?. Arthritis Res Ther 3, L017 (2001) doi:10.1186/ar162

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Keywords

  • Public Health
  • Rheumatoid Arthritis
  • Immune Response
  • Arthritis
  • Monoclonal Antibody