Zanotti Sergio, Kumar Aseem, Kumar Anand
Section of Critical Care Medicine, Rush-Presbyterian-St. Luke's Medical Center, Room 214 Jones, 1635 west Congress Parkway, Chicago, Illinois 60612, USA.
Expert Opin Investig Drugs. 2002 Aug;11(8):1061-75. doi: 10.1517/13543784.11.8.1061.
Sepsis and septic shock are a major cause of morbidity and mortality in patients admitted to the intensive care unit. Since the introduction of antibiotic therapy, the mortality associated with sepsis has remained within the 30- 50% range. Sepsis constitutes the systemic response to infection. This response encompasses both pro-inflammatory and anti-inflammatory phases that are marked by the sequential generation of pro- and anti-inflammatory cytokines. Among the most important pro-inflammatory cytokines are TNF-alpha and IL-1beta. The pro-inflammatory effects of such cytokines are inhibited by soluble receptors/receptor antagonists and anti-inflammatory cytokines including IL-10 and transforming growth factor-beta. Modulation of the activity of both pro- and anti-inflammatory cytokines to improve outcome in patients with sepsis has been subject of multiple clinical studies. This review will examine clinical trials evaluating several strategies for blocking or attenuating TNF-alpha and IL-1beta activity. This review will also survey the current state of experimental therapies involving IL-10, transforming growth factor-beta, granulocyte colony-stimulating factor and IFN-phi. Finally, newer developments related to less known cytokines such as macrophage migration inhibitory factor and high mobility group 1 protein will be evaluated.
脓毒症和脓毒性休克是重症监护病房患者发病和死亡的主要原因。自引入抗生素治疗以来，与脓毒症相关的死亡率一直保持在30%至50%之间。脓毒症是机体对感染的全身性反应。这种反应包括促炎和抗炎阶段，其特征是促炎和抗炎细胞因子的相继产生。其中最重要的促炎细胞因子是肿瘤坏死因子-α和白细胞介素-1β。此类细胞因子的促炎作用受到可溶性受体/受体拮抗剂以及包括白细胞介素-10和转化生长因子-β在内的抗炎细胞因子的抑制。调节促炎和抗炎细胞因子的活性以改善脓毒症患者的预后已成为多项临床研究的主题。本综述将审视评估多种阻断或减弱肿瘤坏死因子-α和白细胞介素-1β活性策略的临床试验。本综述还将概述涉及白细胞介素-10、转化生长因子-β、粒细胞集落刺激因子和干扰素-φ的实验性治疗的现状。最后，将评估与巨噬细胞移动抑制因子和高迁移率族蛋白1等鲜为人知的细胞因子相关的最新进展。
