The clinical relevance of necroinflammation-highlighting the importance of acute kidney injury and the adrenal glands

Research output: Contribution to journalReview articleContributedpeer-review

Contributors

Abstract

Necroinflammation is defined as the inflammatory response to necrotic cell death. Different necrotic cell death pathways exhibit different immune reponses, despite a comparable level of intracellular content release (referred to as damage associated molecular patterns or DAMPs). In addition to DAMP release, which is inevitably associated with necrotic cell death, the active production of pro/anti-inflammatory cytokines characterizes certain necrotic pathways. Necroptosis, ferroptosis and pyroptosis, therefore, are immunogenic to a different extent. In this review, we discuss the clinical relevance of necroinflammation highlighting potential human serum markers. We focus on the role of the adrenal glands and the lungs as central organs affected by systemic and/or local DAMP release and underline their role in intensive care medicine. In addition, data from models of acute kidney injury (AKI) and kidney transplantation have significantly shaped the field of necroinflammation and may be helpful for the understanding of the potential role of dialysis and plasma exchange to treat ongoing necroinflammation upon intensive care unit (ICU) conditions. In conclusion, we are only beginning to understand the importance of necroinflammation in diseases and transplantation, including xenotransplantation. However, given the existing efforts to develop inhibitors of necrotic cell death (ferrostatins, necrostatins, etc), we consider it likely that interference with necroinflammation reaches clinical routine in the near future.

Details

Original languageEnglish
Pages (from-to)68-82
Number of pages15
JournalCell death and differentiation
Volume26
Issue number1
Publication statusPublished - Jan 2019
Peer-reviewedYes

External IDs

PubMedCentral PMC6294800
Scopus 85053464036
ORCID /0000-0003-2739-345X/work/145696875
ORCID /0000-0001-6287-9725/work/145698893
ORCID /0000-0002-9728-1413/work/145699159

Keywords

Sustainable Development Goals

Keywords

  • Acute Kidney Injury/immunology, Adrenal Glands/blood supply, Alarmins/immunology, Animals, Biomarkers/blood, Caspases/metabolism, Cytokines/metabolism, Ferroptosis, Humans, Inflammation/blood, Lipid Peroxidation, Mice, Necrosis/blood, Pyroptosis/immunology, Transplantation, Heterologous