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

Amaral, F. A., Fagundes, C. T., Liew, F. Y., Souza, A. L. S., Souza, D. G., Teixeira, M. M., Vieira, A. T. and Xu, D. (2007) ST2, an IL-1R family member, attenuates inflammation and lethality after intestinal ischemia and reperfusion. Journal of Leukocyte Biology, 81, pp. 492-499. (doi: 10.1189/jlb.0606422)

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Publisher's URL: http://dx.doi.org/10.1189/jlb.0606422

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 production of TNF-α 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-α 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Xu, Dr Damo
Authors: Amaral, F. A., Fagundes, C. T., Liew, F. Y., Souza, A. L. S., Souza, D. G., Teixeira, M. M., Vieira, A. T., and Xu, D.
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 Leukocyte Biology
Publisher:Federation of American Societies for Experimental Biology
ISSN:0741-5400
ISSN (Online):1938-3673
Published Online:10 November 2006
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
241511Characterisation of genes differentially expressed on subsets of T lymphocytesFoo LiewMedical Research Council (MRC)G9818261Infection Immunity and Inflammation Medicine