Terblanche Marius, Almog Yaniv, Rosenson Robert S, Smith Terry S, Hackam Daniel G
Department of Critical Care Medicine, St Thomas' Hospital, London, UK.
Lancet Infect Dis. 2007 May;7(5):358-68. doi: 10.1016/S1473-3099(07)70111-1.
Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing cause of mortality worldwide. Animal and human observational studies suggest statins may prevent the morbidity and mortality associated with the sepsis syndrome. In this Review, we describe the demonstrated mechanisms through which statins modulate the inflammatory response associated with sepsis. These mechanisms include effects on cell signalling with consequent changes at the transcriptional level, the induction of haem oxygenase, the direct alteration of leucocyte-endothelial cell interaction, and the reduced expression of MHC II. Since statins do not target individual inflammatory mediators, but possibly reduce the overall magnitude of the systemic response, this effect could prove an important distinguishing feature modulating the host response to septic insults. This work establishes the biological plausibility needed for future trials of statins in critical illness.
脓毒症是一种由感染引起的炎症综合征，是全球范围内导致死亡的主要且日益增加的原因。动物和人类观察性研究表明，他汀类药物可能预防与脓毒症综合征相关的发病率和死亡率。在本综述中，我们描述了他汀类药物调节与脓毒症相关的炎症反应的已证实机制。这些机制包括对细胞信号传导的影响以及随之而来的转录水平变化、血红素加氧酶的诱导、白细胞与内皮细胞相互作用的直接改变，以及主要组织相容性复合体II类分子表达的降低。由于他汀类药物并非针对个别炎症介质，而是可能降低全身反应的总体强度，这一效应可能是调节宿主对脓毒症刺激反应的一个重要区别特征。这项工作为未来他汀类药物在危重病中的试验奠定了生物学合理性基础。
