Division of Nephrology, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
Biotechnology Center (BIOTEC), Technical University Dresden, Dresden, Germany.
Cell Death Differ. 2019 Jan;26(1):68-82. doi: 10.1038/s41418-018-0193-5. Epub 2018 Sep 17.
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.
坏死性炎症被定义为对坏死细胞死亡的炎症反应。尽管细胞内内容物释放水平相当（称为损伤相关分子模式或 DAMPs），但不同的坏死细胞死亡途径表现出不同的免疫反应。除了不可避免地与坏死细胞死亡相关的 DAMPs 释放外，某些坏死途径还会主动产生促炎/抗炎细胞因子。因此，细胞坏死、铁细胞坏死和细胞焦亡在不同程度上具有免疫原性。在这篇综述中，我们讨论了坏死性炎症的临床相关性，强调了潜在的人类血清标志物。我们重点讨论了肾上腺和肺作为受全身和/或局部 DAMPs 释放影响的中心器官的作用，并强调了它们在重症监护医学中的作用。此外，急性肾损伤 (AKI) 和肾移植模型的数据极大地推动了坏死性炎症领域的发展，对于理解透析和血浆置换在重症监护病房 (ICU) 条件下治疗持续坏死性炎症的潜在作用可能有所帮助。总之，我们才刚刚开始了解坏死性炎症在疾病和移植（包括异种移植）中的重要性。然而，鉴于目前正在努力开发坏死细胞死亡抑制剂（铁细胞抑制剂、坏死细胞抑制剂等），我们认为在不久的将来，干预坏死性炎症很可能会进入临床常规。
