Division of Research, Critical Care, and Acute Care Surgery, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Division of Podiatric Medicine and Surgery, Critical Care, and Acute Care Surgery, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Surg Infect (Larchmt). 2020 Nov;21(9):732-744. doi: 10.1089/sur.2019.363. Epub 2020 Apr 2.
Sepsis is defined as a dysregulated host response to infection, resulting in life-threatening organ dysfunction. It is now understood that this dysregulation not only constitutes excessive inflammation, but also sustained immune suppression. Immune-modulatory therapies thus have great potential for novel sepsis therapies. Here, we provide a review of biomarkers and functional assays designed to immunologically stage patients with sepsis as well as therapies designed to alter the innate and adaptive immune systems of patients with sepsis beneficially. A search of PubMed/MEDLINE and clinicaltrials.gov was performed between October 1, 2019 and December 22, 2019 using search terms such as "sepsis immunotherapy," "sepsis biomarkers," "sepsis clinical trials," and variations thereof. Despite more than 30 years of research, there is still no Food and Drug Administration (FDA)-cleared biomarker that has proven to be effective in either identifying patients with sepsis who are at an increased risk of adverse outcomes or responsive to specific interventions. Similarly, past clinical trials investigating new treatment strategies have rarely stratified patients with sepsis. Overall, the results of these trials have been disappointing. Novel efforts to properly gauge an individual patient's immune response and choose an appropriate immunomodulatory agent based on the results are underway. Our evolving understanding of the different mechanisms perturbing immune homeostasis during sepsis strongly suggests that future successes will depend on finding the right therapy for the right patient and administering it at the right time. For such a personalized medicine approach, novel biomarkers and functional assays to properly stage the patient with sepsis will be crucial. The growing repertoire of immunomodulatory agents at our disposal, as well as re-appraisal of agents that have already been tested in unstratified cohorts of patients with sepsis, may finally translate into successful treatment strategies for sepsis.
脓毒症是指宿主对感染的失调反应，导致危及生命的器官功能障碍。现在人们已经认识到，这种失调不仅构成了过度的炎症，还持续存在免疫抑制。因此，免疫调节疗法在新型脓毒症治疗方面具有巨大的潜力。在这里，我们提供了对生物标志物和功能检测的综述，这些标志物和功能检测旨在对脓毒症患者进行免疫学分期，以及旨在改变脓毒症患者固有和适应性免疫系统的治疗方法。在 2019 年 10 月 1 日至 2019 年 12 月 22 日期间，我们使用了“脓毒症免疫疗法”、“脓毒症生物标志物”、“脓毒症临床试验”等搜索词，在 PubMed/MEDLINE 和 clinicaltrials.gov 上进行了搜索。尽管经过 30 多年的研究，仍然没有经过食品和药物管理局（FDA）批准的生物标志物被证明可以有效地识别处于不良预后风险增加的脓毒症患者或对特定干预措施有反应的患者。同样，过去研究新治疗策略的临床试验很少对脓毒症患者进行分层。总的来说，这些试验的结果令人失望。目前正在进行新的努力，以正确评估个体患者的免疫反应，并根据结果选择合适的免疫调节剂。我们对脓毒症期间扰乱免疫平衡的不同机制的不断认识强烈表明，未来的成功将取决于为正确的患者找到正确的治疗方法，并在正确的时间进行治疗。对于这种个性化医疗方法，正确分期脓毒症患者的新型生物标志物和功能检测将是至关重要的。我们现在可以使用越来越多的免疫调节剂，以及重新评估已经在未分层的脓毒症患者队列中进行测试的药物，这可能最终会转化为成功的脓毒症治疗策略。
