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

被引：445

作者：

Hotchkiss, RS ^{[1
]}

Chang, KC

Swanson, PE

Tinsley, KW

Hui, JJ

Klender, P

Xanthoudakis, S

Roy, S

Black, C

Grimm, E

Aspiotis, R

Han, Y

Nicholson, DW

Karl, IE

机构：

[1] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Comparat Med, St Louis, MO 63110 USA

[5] Merck Frosst Ctr Therapeut Res, Dept Biochem, Pointe Claire, PQ H9R 4P8, Canada

[6] Merck Frosst Ctr Therapeut Res, Dept Mol Biol, Pointe Claire, PQ H9R 4P8, Canada

[7] Merck Frosst Ctr Therapeut Res, Dept Med Chem, Pointe Claire, PQ H9R 4P8, Canada

来源：

NATURE IMMUNOLOGY | 2000年 / 1卷 / 06期

关键词：

D O I：

10.1038/82741

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-I-/- 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.

引用

页码：496 / 501

页数：6