title: [Mouse models for rheumatoid arthritis and their use in drug development].
abstract: Rheumatoid arthritis (RA) is a serious medical problem, with approximately 1% of the people in the world affected. The disease is autoimmune in nature and characterized by chronic inflammation of the synovial tissue in multiple joints, which leads to joint destruction, although the etiopathogenesis has not been elucidated completely. It is remarkable that expression of inflammatory cytokines is augmented in the joints. We previously reported on an inflammatory arthropathy resembling RA that develops in high incidence among transgenic (Tg) mice that carry the human T cell leukemia virus type I (HTLV-I) tax gene. Autoimmune pathogenesis was suggested in this RA model, and levels of cytokines including IL-1 were elevated in the joints of these Tg mice. Depletion of IL-1 by gene targeting greatly reduced the incidence of the disease, indicating the importance of this cytokine in the development of arthritis. Furthermore, IL-1 receptor antagonist (IL-1Ra)-deficient mice develop autoimmunity and arthritis spontaneously. These observations suggest that excess IL-1 signaling causes autoimmunity. We show that IL-1 activates the immune system non-specifically by inducing CD40L and OX40 co-signaling molecules on T cells. In this review, the roles of IL-1 in the development of autoimmunity and arthritis will be discussed in correlation with the development of new drugs.
authors.affiliation: Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. iwakura@ims.u-tokyo.ac.jp
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D007375:Interleukin-1