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 antiinflammatory. 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 doseresponse 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.
Yeager, Mark P; Pioli, Patricia A; and Guyre, Paul M
"CORTISOL EXERTS BI-PHASIC REGULATION OF INFLAMMATION IN HUMANS,"
Dose-Response: An International Journal: Vol. 9
, Article 5.
Available at: https://scholarworks.umass.edu/dose_response/vol9/iss3/5