Document Type


Publication Date


Publication Title

Dose-Response - A Publication of International Hormesis Society


Geisel School of Medicine


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.



Original Citation

Yeager MP, Pioli PA, Guyre PM. Cortisol exerts bi-phasic regulation of inflammation in humans. Dose Response. 2011;9(3):332-47. doi: 10.2203/dose-response.10-013.Yeager. Epub 2010 Aug 12. PMID: 22013396; PMCID: PMC3186928.