Molecular ImmunoRheumatology, INSERM UMR_S1109, Laboratory of Excellence Transplantex, University of Strasbourg, Strasbourg, France.
German Academy for Transplantation Medicine, Munich, Germany.
Mol Diagn Ther. 2020 Jun;24(3):251-262. doi: 10.1007/s40291-020-00460-z.
This opinion article discusses the increasing attention paid to the role of activating damage-associated molecular patterns (DAMPs) in initiation of inflammatory diseases and suppressing/inhibiting DAMPs (SAMPs) in resolution of inflammatory diseases and, consequently, to the future roles of these novel biomarkers as therapeutic targets and therapeutics. Since controlled production of DAMPs and SAMPs is needed to achieve full homeostatic restoration and repair from tissue injury, only their pathological, not their homeostatic, concentrations should be therapeutically tackled. Therefore, distinct caveats are proposed regarding choosing DAMPs and SAMPs for therapeutic purposes. For example, we discuss the need to a priori identify and define a context-dependent "homeostatic DAMP:SAMP ratio" in each case and a "homeostatic window" of DAMP and SAMP concentrations to guarantee a safe treatment modality to patients. Finally, a few clinical examples of how DAMPs and SAMPs might be used as therapeutic targets or therapeutics in the future are discussed, including inhibition of DAMPs in hyperinflammatory processes (e.g., systemic inflammatory response syndrome, as currently observed in Covid-19), administration of SAMPs in chronic inflammatory diseases, inhibition of SAMPs in hyperresolving processes (e.g., compensatory anti-inflammatory response syndrome), and administration/induction of DAMPs in vaccination procedures and anti-cancer therapy.
这篇观点文章讨论了人们对激活损伤相关分子模式（DAMPs）在炎症性疾病发生中的作用以及抑制/抑制 DAMPs（SAMPs）在炎症性疾病消退中的作用的日益关注，因此，这些新型生物标志物作为治疗靶点和治疗剂的未来作用。由于需要控制 DAMPs 和 SAMPs 的产生，才能从组织损伤中实现完全的体内平衡恢复和修复，因此仅应针对其病理性而非生理性浓度进行治疗。因此，针对治疗目的选择 DAMPs 和 SAMPs 时提出了一些注意事项。例如，我们讨论了在每种情况下都需要事先确定和定义与上下文相关的“体内平衡 DAMPs：SAMP 比”，以及 DAMPs 和 SAMP 浓度的“体内平衡窗口”，以保证为患者提供安全的治疗方式。最后，讨论了 DAMPs 和 SAMPs 将来如何可能被用作治疗靶点或治疗剂的一些临床示例，包括在过度炎症过程中抑制 DAMPs（例如全身性炎症反应综合征，如目前在 Covid-19 中观察到的那样），在慢性炎症性疾病中给予 SAMPs，在过度消退过程中抑制 SAMPs（例如代偿性抗炎反应综合征），以及在疫苗接种程序和抗癌治疗中给予/诱导 DAMPs。
