Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York-Presbyterian Hospital-Weill Cornell Medicine, New York, NY, USA; email:
Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; email:
Annu Rev Physiol. 2022 Feb 10;84:157-181. doi: 10.1146/annurev-physiol-061121-040214. Epub 2021 Oct 27.
Sepsis is expected to have a substantial impact on public health and cost as its prevalence increases. Factors contributing to increased prevalence include a progressively aging population, advances in the use of immunomodulatory agents to treat a rising number of diseases, and immune-suppressing therapies in organ transplant recipients and cancer patients. It is now recognized that sepsis is associated with profound and sustained immunosuppression, which has been implicated as a predisposing factor in the increased susceptibility of patients to secondary infections and mortality. In this review, we discuss mechanisms of sepsis-induced immunosuppression and biomarkers that identify a state of impaired immunity. We also highlight immune-enhancing strategies that have been evaluated in patients with sepsis, as well as therapeutics under current investigation. Finally, we describe future challenges and the need for a new treatment paradigm, integrating predictive enrichment with patient factors that may guide the future selection of tailored immunotherapy.
脓毒症的发病率不断上升,预计会对公共卫生和医疗成本造成重大影响。导致发病率上升的因素包括人口老龄化、免疫调节剂在治疗不断增加的疾病中的应用进展,以及器官移植受者和癌症患者的免疫抑制治疗。现在人们认识到,脓毒症与深刻而持续的免疫抑制有关,这被认为是患者易发生继发感染和死亡的一个易感因素。在这篇综述中,我们讨论了脓毒症引起免疫抑制的机制以及识别免疫受损状态的生物标志物。我们还强调了已在脓毒症患者中评估的免疫增强策略,以及当前正在研究的治疗方法。最后,我们描述了未来的挑战和对新的治疗模式的需求,将预测性富集与可能指导未来个体化免疫治疗选择的患者因素相结合。