Bi-phasic Regulation of Inflammation by Cortisol

Mark Yeager, a director of research in the Department of Anesthesiology and Critical Care Medicine at Dartmouth-Hitchcock Medical Center, recently published an article in Formerly Nonlinearity in Biology, Toxicology, and Medicine. In his article, he presents a new paradigm for the properties of cortisol as an anti-inflammatory agent.

Glucocorticoids (GCs) are a class of steroids that have been found to suppress inflammation in humans. Research by Hench et al., first published in 1949, spurred numerous studies in the biomedical field of the suppressive properties of various GCs. Recently, research has focused on the stimulatory properties of these steroids.

Yeager’s team investigated the glucocorticoid cortisol, which is released by the adrenal glands in response to stress.  The results established three theories about the properties of cortisol.

First, in the in vivo human studies, it was shown that diurnal (baseline) concentrations of cortisol do not have an anti-inflammatory effect.  Healthy human subjects were treated with an antagonist that depletes endogenous cortisol activity.  Cells were then taken from these humans and stimulated with bacterial lipopolysaccharides to induce inflammation.  These cells lacking in cortisol remained inflamed.

Secondly, cortisol was shown to exert an anti-inflammatory effect in humans when the levels were varied up to 10 nanomol of cortisol.  Lastly Yeager demonstrated that pre-treating humans with cortisol before surgery resulted in a bi-phasic response later.  An intermediate amount of cortisol increased the inflammation, while a high amount had no effect on the surgical inflammation  (see Fig. 1). From these results, the team concluded that cortisol regulation of inflammation is dynamic – the effects change over time – and dualistic – it can both augment and reduce inflammation.

Yeager’s findings have altered the traditional theory that glucocorticoids exert an anti-inflammatory effect with a linear dose-response relationship.  Past research has concluded that too little GCs results in continued inflammation and too much impairs processes that repair injured tissue and prevent infection.  However, this new study has found a non-linear pattern based on the effects cortisol exerts in vivo on humans.  Future studies should focus on other common GCs to see if the results are duplicated.