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6793454 
Journal Article 
Apoptosis and caspases regulate death and inflammation in sepsis 
Hotchkiss, RS; Nicholson, DW; , 
2006 
1 
Nature Reviews. Immunology
ISSN: 1474-1733
EISSN: 1474-1741 
NATURE PUBLISHING GROUP 
LONDON 
813-822 
17039247 
WOS:000241574000012 
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.