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Nat Rev Immunol. 2006 Nov;6(11):813-22. Epub 2006 Oct 13.

Apoptosis and caspases regulate death and inflammation in sepsis.

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Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 South Euclid, St Louis, Missouri 63110, USA.


Although the prevailing concept has been that mortality in sepsis results from an unbridled hyper-inflammatory cytokine-mediated response, the failure of more than 30 clinical trials to treat sepsis by controlling this cytokine response requires a 'rethink' of the molecular mechanism underpinning the development of sepsis. As we discuss here, remarkable new studies indicate that most deaths from sepsis are actually the result of a substantially impaired immune response that is due to extensive death of immune effector cells. Rectification of this apoptotic-inflammatory imbalance using modulators of caspases and other components of the cell-death pathway have shown striking efficacy in stringent animal models of sepsis, indicating an entirely novel path forward for the clinical treatment of human sepsis.

[Indexed for MEDLINE]

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