title: Peroxiredoxin 1 induces inflammatory cytokine response and predicts outcome of cardiogenic shock patients necessitating extracorporeal membrane oxygenation: an observational cohort study and translational approach.
abstract: Extracellular peroxiredoxin 1 (Prdx1) has been implicated to play a pivotal role in regulating inflammation; however, its function in tissue hypoxia-induced inflammation, such as severe cardiogenic shock patients, has not yet been defined. Thus, the objective of this study was to test the hypothesis that Prdx1 possesses prognostic value and instigates systemic inflammatory response syndrome in cardiogenic shock patients undergoing extracorporeal membrane oxygenation (ECMO) support.
  
  
  
  We documented the early time course evolution of circulatory Prdx1, hypoxic marker carbonic anhydrase IX, inflammatory cytokines including IL-6, IL-8, IL-10, MCP-1, TNF-α, IL-1β, and danger signaling receptors (TLR4 and CD14) in a cohort of cardiogenic shock patients within 1 day after ECMO support. In vitro investigations employing cultured murine macrophage cell lines and human monocytes were applied to clarify the relationship between Prdx1 and inflammatory response.
  
  
  
  Prdx1 not only peaked earlier than all the other cytokines we studied during the initial course, but also predicted a worse outcome in patients who had higher initial Prdx1 plasma levels. The Prdx1 levels in patients positively correlated with hypoxic markers carbonic anhydrase IX and lactate, and inflammatory cytokines. In vitro study demonstrated that hypoxia/reoxygenation induced Prdx1 release from human monocytes and enhanced the responsiveness of the monocytes in Prdx1-induced cytokine secretions. Furthermore, functional inhibition by Prdx1 antibody implicated a crucial role of Prdx1 in hypoxia/reoxygenation-induced IL-6 secretion.
  
  
  
  Prdx1 release during the early phase of ECMO support in cardiogenic shock patients is associated with the development of systemic inflammatory response syndrome and poor clinical outcomes. Thus, circulating Prdx1 provides not only prognostic information but may be a promising target against ischemia/reperfusion injury.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.|Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Chia-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Shuenn-Wen
authors.initials: SW
authors.lastname: Kuo
authors.affiliation: Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Hsu
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Shu-Chien
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Pi-Ru
authors.initials: PR
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Yih-Sharng
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. jouts@ntu.edu.tw.|College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. jouts@ntu.edu.tw.
authors.forename: Tzuu-Shuh
authors.initials: TS
authors.lastname: Jou
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC. kowj@ntu.edu.tw.|Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan, ROC. kowj@ntu.edu.tw.|College of Medicine, National Taiwan University, Taipei, Taiwan, ROC. kowj@ntu.edu.tw.
authors.forename: Wen-Je
authors.initials: WJ
authors.lastname: Ko
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000150:complications; D018836:Inflammation Mediators / Q000097:blood*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D054464:Peroxiredoxins / Q000097:blood*; D011379:Prognosis; D012770:Shock, Cardiogenic / Q000097:blood* / Q000628:therapy*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D051197:Toll-Like Receptor 4; D054464:Peroxiredoxins
keywords: Cardiogenic shock; Danger-associated molecular patterns; Extracorporeal membrane oxygenation; Ischemia-reperfusion; Peroxiredoxin 1; Systemic inflammatory response syndrome