Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18

Wei, X.-q., Leung, B. P., Arthur, H. M. L., Liew, F. Y. and McInnes, I. B. (2001) Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. Journal of Immunology, 166, pp. 517-521. (doi:10.4049/jimmunol.166.1.517) (PMID:11123331)

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Abstract

We have recently reported the presence and a potential proinflammatory role of IL-18 in the synovium of patients with rheumatoid arthritis. To obtain direct evidence that IL-18 plays an influential role in articular inflammation, we investigated the development of collagen-induced arthritis in a strain of mice lacking IL-18 (IL-18−/−) of DBA/1 background. IL-18−/− mice developed markedly reduced incidence of arthritis compared with heterozygous or wild-type mice. Of the IL-18−/− mice that developed arthritis, the severity of the disease was significantly reduced compared with the intact mice. This was accompanied by reduced articular inflammation and destruction evident on histology. IL-18−/− mice also had significantly reduced Ag-specific proliferation and proinflammatory cytokine (IFN-γ, TNF-α, IL-6, and IL-12) production by spleen and lymph node cells in response to bovine type II collagen (CII) in vitro compared with wild-type mice, paralleled in vivo by a significant reduction in serum anti-CII IgG2a Ab level. Treatment with rIL-18 completely reversed the disease of the IL-18−/− mice to that of the wild-type mice. These data directly demonstrate a pivotal role of IL-18 in the development of inflammatory arthritis and suggest that antagonists to IL-18 may have therapeutic potential in rheumatic diseases.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Professor Foo and Arthur, Ms Helen and Leung, Dr Bernard
Authors: Wei, X.-q., Leung, B. P., Arthur, H. M. L., Liew, F. Y., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Immunology

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