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Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte.
- Source :
-
Nature immunology [Nat Immunol] 2000 Dec; Vol. 1 (6), pp. 496-501. - Publication Year :
- 2000
-
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.
- Subjects :
- Adoptive Transfer
Animals
Bacteremia drug therapy
Bacteremia microbiology
Bacteremia pathology
Caspase 3
Caspases genetics
Colony Count, Microbial
Female
Homeodomain Proteins genetics
Homeodomain Proteins metabolism
Humans
In Vitro Techniques
Interferon-gamma biosynthesis
Interleukin-2 biosynthesis
Lymphocytes pathology
Mice
Mice, Knockout
Sepsis pathology
Apoptosis drug effects
Caspase Inhibitors
Cysteine Proteinase Inhibitors pharmacology
Lymphocytes drug effects
Sepsis drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2908
- Volume :
- 1
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 11101871
- Full Text :
- https://doi.org/10.1038/82741