A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST21

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A Novel Therapy of Murine Collagen-Induced Arthritis with Soluble T1/ST21

http://www.jimmunol.org/cgi/content/abstract/173/1/145

The Journal of Immunology, 2004, 173: 145-150.

Copyright © 2004 by The American Association of Immunologists

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. 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-. Spleen cells from the sST2-Fc-treated mice produced

significantly less IFN-, TNF-, 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- when cocultured with

peripheral blood T cells from rheumatoid patients.

Together these results demonstrate that sST2-Fc may provide a novel

approach in treating chronic autoimmune conditions by inhibiting the

release of proinflammatory cytokines.

Bernard P. Leung2,*, Damo Xu*, Shauna Culshaw*, Iain B. McInnes and Foo

Y. Liew3,*

* Division of Immunology, Infection, and Inflammation and Centre for

Rheumatic Diseases, Royal Infirmary, University of Glasgow, Glasgow,

United Kingdom