Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Published online before print November 10, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0606422

Received for publication June 30, 2006.
Revised August 2, 2006.
Accepted for publication August 21, 2006.

Article

ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion

Caio T. Fagundes *, Flávio A. Amaral *, Adriano L. S. Souza *, Angélica T. Vieira *, Damo Xu {dagger}, Foo Y. Liew {dagger}, Danielle G. Souza *{ddagger}, and Mauro M. Teixeira *@

Departamentos de *Bioquímica e Imunologia and {ddagger}Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; and {dagger}Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK

@ To whom correspondence should be addressed. E-mail: mmtex{at}mono.icb.ufmg.br.


  Abstract

Ischemia reperfusion injury is characterized by local and systemic inflammation leading to considerable mortality. Previously, we have reported that soluble T1/ST2 (sST2), a member of the IL-1 receptor gene family, inhibits LPS-induced macrophage proinflammatory cytokine production. Here, we report the therapeutic effect of sST2-Fc in a murine model of intestinal ischemia reperfusion-induced injury. Administration of sST2-Fc fusion protein i.v., 10 min before reperfusion, reduced the TNF-{alpha} dose-dependently in the intestine and in the lungs. The sST2-Fc treatment with the highest dose (100 µg) resulted in inhibited vascular permeability, neutrophilia, and hemorrhage in the intestine and the lungs compared with controls treated with normal IgG. This was associated with down-regulated tissue levels of proinflammatory cytokines, markedly reduced serum TNF-{alpha} levels, and increased survival of mice from the sST2-Fc-treated group after ischemia and reperfusion injury. The beneficial effect of sST2-Fc treatment was associated with elevated IL-10 production in intestine and lung. sST2-Fc was not able to prevent the inflammatory response associated with intestinal ischemia and reperfusion in IL-10-deficient mice, suggesting that sST2 exerts its anti-inflammatory effect in a IL-10-dependent manner. These results also demonstrate that sST2-Fc may provide a novel, complementary approach in treating ischemic reperfusion injury.

Key Words: neutrophil influx • IL-10 • TNF-{alpha}






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Copyright © 2006 by the Society for Leukocyte Biology.