Peroxiredoxin 1 induces inflammatory cytokine response and predicts outcome of cardiogenic shock patients necessitating extracorporeal membrane oxygenation: an observational cohort study and translational approach

Journal of Translational Medicine

Research

Shu-Chien Huang¹  Chih-Hsien Wang¹  Yih-Sharng Chen¹  Pi-Ru Tsai¹  Shuenn-Wen Kuo¹  Wen-Je Ko²  Li-Ming Hsu³  Tzuu-Shuh Jou⁴  Chia-Hsiung Liu⁵ 

[1] Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC;Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC;Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan, ROC;College of Medicine, National Taiwan University, Taipei, Taiwan, ROC;Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan, ROC;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC;College of Medicine, National Taiwan University, Taipei, Taiwan, ROC;Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC;Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC;

关键词: Extracorporeal membrane oxygenation;    Cardiogenic shock;    Peroxiredoxin 1;    Danger-associated molecular patterns;    Ischemia-reperfusion;    Systemic inflammatory response syndrome;   

DOI  :  10.1186/s12967-016-0869-x

 received in 2015-12-28, accepted in 2016-04-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundExtracellular 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.MethodsWe 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.ResultsPrdx1 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.ConclusionsPrdx1 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.

【 授权许可】

CC BY   
© Liu et al. 2016