Journal
DOSE-RESPONSE
Volume 9, Issue 3, Pages 332-347Publisher
SAGE PUBLICATIONS INC
DOI: 10.2203/dose-response.10-013.Yeager
Keywords
Glucocorticoid; cortisol inflammation; innate immunity; bi-phasic; endotoxemia
Funding
- National Institutes of Health, NIAID [AI051547]
- NATIONAL CANCER INSTITUTE [P30CA023108] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI090578, R01AI051547] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available