The aim of the project is to test the hypothesis that, in chronic arthritis, a polarised Thl response drives articular disease and is followed by a protective Th2 response that mediates extra-articular disease. In order to do so, a chronic relapsing form of collagen-induced arthritis in mice will be developed that more closely resembles rheumatoid arthritis than the model induced with bovine type II collagen (CII), which is a self-limiting disease. DBA/1 mice will be immunised with mouse CII, which is known to induce chronic arthritis. Alternatively (and more conveniently), mice will be immunised with a DNA plasmid encoding mouse CII.
Chronic relapsing disease will be described in detail: clinical course, extra-articular disease, joint histology, phenotype of synovial cells and cytokine production by the synovium and lymph nodes. In addition, Th 1 or Th2 responses will be manipulated with cytokines or antibodies, such as IL-4, IL-12 or anti-IL-12.
A chronic murine model of arthritis will provide a highly valuable tool for studying pathogenesis and therapy of rheumatoid arthritis.