Apoptosis and caspases regulate death and inflammation in sepsis

Richard S. Hotchkiss, Donald W. Nicholson

Research output: Contribution to journalReview articlepeer-review

647 Scopus citations


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.

Original languageEnglish
Pages (from-to)813-822
Number of pages10
JournalNature Reviews Immunology
Issue number11
StatePublished - Nov 13 2006


Dive into the research topics of 'Apoptosis and caspases regulate death and inflammation in sepsis'. Together they form a unique fingerprint.

Cite this