Cardiac arrest and resuscitation activates the hypothalamic-pituitary-adrenal axis and results in severe immunosuppression. Issue 5 (May 2021)

• Record Type: Journal Article
• Authors: Zhao, Qiang; Shen, Yuntian; Li, Ran; Wu, Jiangbo; Lyu, Jingjun; Jiang, Maorong; Lu, Liping; Zhu, Minghua; Wang, Wei; Wang, Zhuoran; Liu, Qiang; Hoffmann, Ulrike; Karhausen, Jörn; Sheng, Huaxin; Zhang, Weiguo; Yang, Wei
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 41:Issue 5(2021)
• Page Start: 1091
• Page End: 1102
• Publication Date: 2021-05
• Subjects: Cardiac arrest -- resuscitation -- immune response -- immunosuppression -- HPA; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X20948612
• Languages: English
• ISSNs: 0271-678X

Abstract

In patients who are successfully resuscitated after initial cardiac arrest (CA), mortality and morbidity rates are high, due to ischemia/reperfusion injury to the whole body including the nervous and immune systems. How the interactions between these two critical systems contribute to post-CA outcome remains largely unknown. Using a mouse model of CA and cardiopulmonary resuscitation (CA/CPR), we demonstrate that CA/CPR induced neuroinflammation in the brain, in particular, a marked increase in pro-inflammatory cytokines, which subsequently activated the hypothalamic-pituitary-adrenal (HPA) axis. Importantly, this activation was associated with a severe immunosuppression phenotype after CA. The phenotype was characterized by a striking reduction in size of lymphoid organs accompanied by a massive loss of immune cells and reduced immune function of splenic lymphocytes. The mechanistic link between post-CA immunosuppression and the HPA axis was substantiated, as we discovered that glucocorticoid treatment, which mimics effects of the activated HPA axis, exacerbated post-CA immunosuppression, while RU486 treatment, which suppresses its effects, significantly mitigated lymphopenia and lymphoid organ atrophy and improved CA outcome. Taken together, targeting the HPA axis could be a viable immunomodulatory therapeutic to preserve immune homeostasis after CA/CPR and thus improve prognosis of post-resuscitation CA patients.