Apoptosis and caspases regulate death and inflammation in sepsis

Nat Rev Immunol. 2006 Nov;6(11):813-22. doi: 10.1038/nri1943. Epub 2006 Oct 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis* / immunology
  • Caspase Inhibitors
  • Caspases / metabolism*
  • Cell Communication
  • Humans
  • Inflammation / enzymology
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / therapy
  • Protease Inhibitors / therapeutic use
  • Sepsis / enzymology*
  • Sepsis / immunology
  • Sepsis / pathology*
  • Sepsis / therapy


  • Caspase Inhibitors
  • Protease Inhibitors
  • Caspases