Children's Health Queensland Clinical Unit, Department of Paediatrics and Child Care, School of Clinical Medicine, Mater Research, Faculty of Medicine, University of Queensland, ST Lucia, Brisbane, QLD, 4078, Australia.
School of Biomedical Sciences, Faculty of Medicine, University of Queensland, ST Lucia, Brisbane, QLD, 4078, Australia.
Inflammation. 2019 Jun;42(3):765-788. doi: 10.1007/s10753-018-0939-8.
Sepsis is a major health problem all over the world. Despite its existence since the time of Hippocrates (470 BC), sepsis is still a serious medical problem for physicians working in both pediatric and adult intensive care units. The most current US FDA-approved drug called recombinant human activated protein C or Drotrecogin-α is also failed in clinical trials and showed similar effects as placebo. The epidemiological data and studies have indicated sepsis as a major socioeconomic burden all over the world. Advances in immunology and genomic medicine have established different immunological mechanisms as major regulators of the pathogenesis of the sepsis. These immunological mechanisms come into action upon activation of several components of the immune system including innate and adaptive immunity. The activation of these immune cells in response to the pathogens or pathogen-associated molecular patterns (PAMPs) responsible for the onset of sepsis is regulated by the metabolic stage of the immune cells called immunometabolism. An alternation in the immunometabolism is responsible for the generation of dysregulated immune response during sepsis and plays a very important role in the process. Thus, it becomes vital to understand the immunometabolic reprograming during sepsis to design future target-based therapeutics depending on the severity. The current review is designed to highlight the importance of immune response and associated immunometabolism during sepsis and its targeting as a future therapeutic approach.
脓毒症是全世界的一个主要健康问题。尽管自希波克拉底时代(公元前 470 年)以来就已经存在脓毒症,但它仍然是儿科和成人重症监护病房医生面临的一个严重的医学问题。目前美国食品和药物管理局批准的唯一药物重组人活化蛋白 C 或依诺肝素-α在临床试验中也失败了,并且与安慰剂的效果相似。流行病学数据和研究表明,脓毒症是全世界的一个主要社会经济负担。免疫学和基因组医学的进展已经确立了不同的免疫机制作为脓毒症发病机制的主要调节剂。这些免疫机制通过激活免疫系统的几个组成部分(包括先天免疫和适应性免疫)发挥作用。这些免疫细胞对病原体或病原体相关分子模式(PAMPs)的激活,负责脓毒症的发生,其受到免疫细胞的代谢状态(称为免疫代谢)的调节。免疫代谢的改变负责在脓毒症期间产生失调的免疫反应,并在该过程中起着非常重要的作用。因此,了解脓毒症期间的免疫代谢重编程,以便根据严重程度设计未来基于靶点的治疗方法变得至关重要。本综述旨在强调脓毒症期间免疫反应和相关免疫代谢的重要性,并将其作为未来的治疗方法进行靶向治疗。