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

Wei, Xiao-Qing, Leung, Bernard P., Arthur, Helen M. L., McInnes, Iain B and Liew, Foo Yew 2001. Reduced incidence and severity of collagen-induced arthritis in mice lacking IL-18. The Journal of Immunology 166 (1) , pp. 517-521.

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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-182/2) of DBA/1 background. IL-182/2 mice developed markedly reduced incidence of arthritis compared with heterozygous or wild-type mice. Of the IL-182/2 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-182/2 mice also had significantly reduced Ag-specific proliferation and proinflammatory cytokine (IFN-g, TNF-a, 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-182/2 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: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 04 Jun 2017 04:16

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