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脓毒症中的免疫紊乱及其治疗是现代重症监护中的一个重大问题。

Immune disorders in sepsis and their treatment as a significant problem of modern intensive care.

作者信息

Łysenko Lidia, Leśnik Patrycja, Nelke Kamil, Gerber Hanna

机构信息

Department of Anaesthesiology and Intensive Therapy, Wroclaw Medical University, Wroclaw, Poland.

Department of Maxillofacial Surgery, Wroclaw Medical University, Wrocław, Poland.

出版信息

Postepy Hig Med Dosw (Online). 2017 Aug 22;71(1):703-712. doi: 10.5604/01.3001.0010.3849.

Abstract

Despite the great advances in the treatment of sepsis over the past 20 years, sepsis remains the main cause of death in intensive care units. In the context of new possibilities of treating sepsis, a comprehensive response of the immune system to the infection, immunosuppression, in particular, has in recent years gained considerable interest. There is vast evidence pointing to the correlation between comorbid immunosuppression and an increased risk of recurrent infections and death. Immune disorders may impact the clinical course of sepsis. This applies in particular to patients with deteriorated clinical response to infections. They usually suffer from comorbidities and conditions accompanied by immunosuppression. Sepsis disrupts innate and adaptive immunity. The key to diagnose the immune disorders in sepsis and undertake targeted immunomodulatory therapy is to define the right biomarkers and laboratory methods, which permit prompt "bedside" diagnosis. Flow cytometry is a laboratory tool that meets these criteria. Two therapeutic methods are currently being suggested to restore the immune homeostasis of sepsis patients. Excessive inflammatory response may be controlled through extracorporeal blood purification techniques, in large part derived from renal replacement therapy. These are such techniques as high-volume haemofiltration, cascade haemofiltration, plasma exchange, coupled plasma filtration and adsorption, high-absorption membranes, high cut-off membranes. The main task of theses techniques is the selective elimination of middle molecular weight molecules, such as cytokines. Pharmacotherapy with the use of such immunostimulants as interleukin 7, granulocyte-macrophage colony-stimulating factor, interferon gamma, PD-1, PD-L1 and CTLA-4 antagonists, intravenous immunoglobulins may help fight immunosuppressive immune disorders.

摘要

尽管在过去20年里脓毒症治疗取得了巨大进展,但脓毒症仍然是重症监护病房的主要死亡原因。在脓毒症治疗新方法不断涌现的背景下,近年来免疫系统对感染的全面反应,尤其是免疫抑制,引起了广泛关注。大量证据表明合并免疫抑制与反复感染及死亡风险增加之间存在关联。免疫紊乱可能影响脓毒症的临床病程。这尤其适用于对感染临床反应恶化的患者。他们通常患有合并症以及伴有免疫抑制的病症。脓毒症会破坏固有免疫和适应性免疫。诊断脓毒症免疫紊乱并进行靶向免疫调节治疗的关键在于确定合适的生物标志物和实验室方法,以便能够迅速进行“床边”诊断。流式细胞术就是一种符合这些标准的实验室工具。目前提出了两种治疗方法来恢复脓毒症患者的免疫稳态。过度的炎症反应可通过体外血液净化技术来控制,这些技术很大程度上源自肾脏替代疗法。包括高容量血液滤过、级联血液滤过、血浆置换、耦合血浆滤过吸附、高吸附膜、高截留膜等技术。这些技术的主要任务是选择性清除中分子量分子,如细胞因子。使用白细胞介素7、粒细胞巨噬细胞集落刺激因子、干扰素γ、PD - 1、PD - L1和CTLA - 4拮抗剂等免疫刺激剂以及静脉注射免疫球蛋白进行药物治疗,可能有助于对抗免疫抑制性免疫紊乱。

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