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Nat Immunol. 2000 Dec;1(6):496-501.

Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte.

Author information

1
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA. hotch@morpheus.wustl.edu

Abstract

Sepsis induces lymphocyte apoptosis and prevention of lymphocyte death may improve the chances of surviving this disorder. We compared the efficacy of a selective caspase-3 inhibitor to a polycaspase inhibitor and to caspase-3-/- mice. Both inhibitors prevented lymphocyte apoptosis and improved survival. Caspase-3-/- mice shared a decreased, but not total, block of apoptosis. The polycaspase inhibitor caused a very substantial decrease in bacteremia. Caspase inhibitors did not benefit RAG-1-/- mice, which had a > tenfold increase in bacteremia compared to controls. Adoptive transfer of T cells that overexpressed the anti-apoptotic protein Bcl-2 increased survival. T cells stimulated with anti-CD3 and anti-CD28 produced increased interleukin 2 and interferon gamma by 6 h. Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection.

PMID:
11101871
DOI:
10.1038/82741
[Indexed for MEDLINE]

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