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Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):341-55.

Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models.

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1
Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. iwakura@ims.u-tokyo.ac.jp

Abstract

Expression of inflammatory cytokines is augmented in the joints of patients with rheumatoid arthritis (RA). We found that cytokine levels are also elevated in the joints of a mouse arthritis model, human T-cell leukemia virus type I (HTLV-I) transgenic (Tg) mouse. 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 the 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 in mouse models will be discussed.

PMID:
12220548
DOI:
10.1016/s1359-6101(02)00021-7
[Indexed for MEDLINE]

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