Volume 5 Supplement 3

3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Open Access

The innate immune system as a therapeutic target in arthritis

  • M Corr1,
  • JY Choe1 and
  • K Pekny1
Arthritis Res Ther20035(Suppl 3):135

https://doi.org/10.1186/ar936

Published: 12 September 2003

Rheumatoid arthritis is a chronic inflammatory disease that may be characterized by several phases. In the initial induction phase of the disease there may be a breech in the normal mechanisms that protect the host from destruction. In the later phase, pathways that are independent of the adaptive immune system may perpetuate inflammation. These pathways may be active in patients who are refractory to biologic therapies that target key cytokines, IL-1 and tumor necrosis factor alpha. The Toll-like receptors (TLRs) are an integral part of the innate immune system, and are present on synovial lining cells, as well as the cells of the immune system, which may amplify their contribution to the inflammatory cascade. We have found that TLR-4 and its coreceptor CD14 can modulate arthritis and can modulate inflammatory joint disease in murine models of arthritis. In particular, exposure to a TLR-4 ligand stimulates release of IL-6 from synovial fibroblast-like cells in culture, and circumvents the requirement for IL-1 receptor signaling in a serum transfer model of arthritis. These data suggest that triggering the innate immune response through the TLRs with either microbial or autologous ligands plays a role in the initiation or perpetuation of rheumatoid arthritis.

Authors’ Affiliations

(1)
Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California San Diego

Copyright

© BioMed Central Ltd 2003

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