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

• Published in: Nature reviews. Immunology Vol. 14; no. 11; pp. 759 - 767
• Main Authors: Linkermann, Andreas, Stockwell, Brent R., Krautwald, Stefan, Anders, Hans-Joachim
• Format: Journal Article Book Review
• Language: English
• Published: London Nature Publishing Group UK 01.11.2014; Nature Publishing Group
• Subjects: 631/250/1932; 631/250/251; 631/250/256; Animals; Apoptosis - immunology; Biomedicine; Causes of; Cell death; Health aspects; Humans; Immunological research; Immunology; Immunosuppression; Immunosuppressive Agents - therapeutic use; Immunotherapy; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Mice; Mitochondria - immunology; Mortality; Multiple organ failure; Multiple Organ Failure - immunology; Multiple Organ Failure - therapy; Necrosis - immunology; Necrosis - therapy; Neoplasms - immunology; Neoplasms - therapy; opinion-2
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/nri3743

In this Opinion article, the authors discuss how the induction of regulated cell death and inflammatory pathways may lead to an auto-amplification loop that causes tissue damage and organ failure. They propose that targeting both processes could be useful for treating a broad range of clinical conditions with an inflammatory basis. 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.