Regulated cell death and inflammation: an auto-amplification loop causes organ failure

Nat Rev Immunol. 2014 Nov;14(11):759-67. doi: 10.1038/nri3743. Epub 2014 Oct 17.


Regulated cell death (RCD) is either immunologically silent or immunogenic. RCD in parenchymal cells may lead to the release of damage- associated molecular patterns that drive both tissue inflammation and the activation of further pathways of RCD. Following an initial event of regulated necrosis, RCD and inflammation can induce each other and drive a local auto-amplification loop that leads to exaggerated cell death and inflammation. In this Opinion article, we propose that such crosstalk between pro-inflammatory and RCD pathways has pathophysiological relevance in solid organ failure, transplantation and cancer. In our opinion, clinicians should not only prescribe immunosuppressive treatments to disrupt this circuit, but also implement the neglected therapeutic option of adding compounds that interfere with RCD.

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Mice
  • Mitochondria / immunology
  • Multiple Organ Failure / immunology*
  • Multiple Organ Failure / therapy*
  • Necrosis / immunology*
  • Necrosis / therapy
  • Neoplasms / immunology
  • Neoplasms / therapy


  • Immunosuppressive Agents