A novel therapy of murine collagen-induced arthritis with soluble T1/ST2

Leung, B.P., Xu, D., Culshaw, S. , McInnes, I. B. and Liew, .Y. (2004) A novel therapy of murine collagen-induced arthritis with soluble T1/ST2. Journal of Immunology, 173(1), pp. 145-150. (doi:10.4049/jimmunol.173.1.145) (PMID:15210768)

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Publisher's URL: http://www.jimmunol.org/cgi/content/abstract/173/1/145

Abstract

Rheumatoid arthritis is characterized by chronic inflammatory infiltration of the synovium, leading to eventual cartilage and bone destruction. Previously, we have reported that soluble T1/ST2 (sST2), a member of the IL-1R gene family, inhibits LPS-induced macrophage proinflammatory cytokine production.<br/> In this study, we report the therapeutic effect of sST2-Fc in the murine model of collagen-induced arthritis. A short term administration of sST2-Fc fusion protein significantly attenuated disease severity compared with controls treated with normal IgG. Histological examination revealed that while control IgG-treated mice developed severe cellular infiltration in the joints, synovial hyperplasia, and joint erosion, this pathology was profoundly reduced in sST2-Fc-treated animals. Treatment of sST2-Fc also down-regulated serum levels of IL-6, IL-12, and TNF-alpha. Spleen cells from the sST2-Fc-treated mice produced significantly less IFN-gamma, TNF-alpha, IL-6, and IL-12 compared with cells from the control mice when cultured with collagen in vitro. Finally, pretreatment with ST2-Fc markedly inhibited the ability of human monocytic THP1 cells to release TNF-alpha when cocultured with peripheral blood T cells from rheumatoid patients.<br/> Together these results demonstrate that sST2-Fc may provide a novel approach in treating chronic autoimmune conditions by inhibiting the release of proinflammatory cytokines.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Culshaw, Professor Shauna
Authors: Leung, B.P., Xu, D., Culshaw, S., McInnes, I. B., and Liew, .Y.
Subjects:Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:Journal of Immunology
ISSN:0022-1767

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