Pyroptotic death storms and cytopenia

Curr Opin Immunol. 2014 Feb;26:128-37. doi: 10.1016/j.coi.2013.12.002. Epub 2013 Dec 22.

Abstract

For over two decades, we have embraced the cytokine storm theory to explain sepsis, severe sepsis and septic shock. The failure of numerous large-scale clinical trials, which aimed to treat sepsis by neutralizing inflammatory cytokines and LPS, indicates that alternative pathophysiological mechanisms are likely to account for sepsis and the associated immune suppression in patients with severe infection. Recent insights that extricate pyroptotic death from inflammatory cytokine production in vivo have highlighted a need to investigate the consequences of apoptotic and non-apoptotic death in contributing to cytopenia and immune suppression. In this review, we will focus on the biochemical and cellular mechanisms controlling pyroptosis, a Caspase-1/11 dependent form of cell death during infection.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Caspase 1 / metabolism
  • Caspases / metabolism
  • Caspases, Initiator
  • Cell Death / immunology
  • Cytophagocytosis / immunology
  • Disease Models, Animal
  • Enzyme Activation / immunology
  • Hematopoietic Stem Cells / enzymology
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Immunocompromised Host
  • Inflammasomes / biosynthesis
  • Inflammasomes / metabolism
  • Interleukin-18 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Mice
  • Necrosis
  • Substrate Specificity / immunology
  • Systemic Inflammatory Response Syndrome / enzymology
  • Systemic Inflammatory Response Syndrome / immunology*
  • Systemic Inflammatory Response Syndrome / pathology*

Substances

  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Casp4 protein, mouse
  • Caspases
  • Caspases, Initiator
  • Caspase 1