Department of Anesthesiology and Critical Care Medicine, Dartmouth-Hitchcock Medical Center.
Dose Response. 2011;9(3):332-47. doi: 10.2203/dose-response.10-013.Yeager. Epub 2010 Aug 12.
Natural and synthetic glucocorticoids (GCs) have been used for decades to suppress inflammation. In this paper, we re-examine the role of the endogenous GC, cortisol, as a primary homeostatic regulator of the human inflammatory response to injury. Our data show that cortisol regulation of innate immunity can be both pro-inflammatory and anti-inflammatory. Using a human model of in vivo cortisol depletion, we first show that baseline (diurnal) cortisol concentrations do not exert an anti-inflammatory effect. This is the first clue that cortisol regulation of inflammation is not represented by a linear dose-response relationship. We next show in surgical patients that cortisol does exert an acute anti-inflammatory effect over a carefully regulated range of physiologic cortisol concentrations. Finally, transient pre-treatment of healthy humans with cortisol induces a bi-phasic response during a later, delayed systemic inflammatory response: an intermediate cortisol concentration augments inflammation while a high cortisol concentration is neither pro- nor anti-inflammatory. Based on these findings and the work of others, we propose a new paradigm that identifies cortisol regulation of human inflammation as both dualistic-it is pro- and anti-inflammatory-and dynamic, it evolves over time.
天然和合成糖皮质激素（GCs）已被使用了几十年，用于抑制炎症。在本文中，我们重新审视了内源性 GC，皮质醇，作为人体对损伤性炎症反应的主要体内平衡调节剂的作用。我们的数据表明，皮质醇对固有免疫的调节既具有促炎作用，也具有抗炎作用。使用体内皮质醇耗竭的人体模型，我们首先表明基线（昼夜）皮质醇浓度不会产生抗炎作用。这是皮质醇对炎症的调节不是呈线性剂量反应关系的第一个线索。接下来，我们在外科患者中表明，在精心调节的生理皮质醇浓度范围内，皮质醇确实会发挥急性抗炎作用。最后，在健康人类中短暂预用皮质醇会在随后的延迟全身炎症反应中引起双相反应：中间皮质醇浓度增强炎症，而高皮质醇浓度既不促进炎症也不抑制炎症。基于这些发现和其他人的工作，我们提出了一个新的范例，该范例将皮质醇对人类炎症的调节确定为双重的 - 既具有促炎作用，也具有抗炎作用 - 并且是动态的，它随着时间的推移而演变。
