Glucocorticoid regulation of the inflammatory response to injury

Authors

  • M. P. Yeager,

    Corresponding author
    1. Departments of 1Anesthesiology and2Physiology, Dartmouth Medical School, Hanover, and Dartmouth-Hitchcock Medical Center, Lebanon, NH
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  • 1 P. M. Guyre,

    1. Departments of 1Anesthesiology and2Physiology, Dartmouth Medical School, Hanover, and Dartmouth-Hitchcock Medical Center, Lebanon, NH
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  • and 2 A. U. Munck 2

    1. Departments of 1Anesthesiology and2Physiology, Dartmouth Medical School, Hanover, and Dartmouth-Hitchcock Medical Center, Lebanon, NH
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  • Supported by NIH grants AI 051547 and AI 053243.

* Mark P. Yeager, MD
Department of Anesthesiology
One Medical Center Drive
Dartmouth-Hitchcock Medical Center
Lebanon
NH 03756
USA
e-mail: mark.p.yeager@hitchcock.org

Abstract

During the first half of the 20th century, physiologists were interested in the adrenal glands primarily because adrenalectomized animals failed to survive even mild degrees of systemic stress. It eventually became clear that hormones secreted by the adrenal cortex were critical for survival and, in this context, adrenal cortical hormones were widely considered to support or stimulate important responses to stress or injury. With the purification and manufacture of adrenal cortical hormones in the 1930s and 1940s, clinicians suddenly discovered the potent anti-inflammatory actions of glucocorticoids (GCs). This dramatic, and unexpected, discovery has dominated clinical and laboratory research into GC actions throughout the second half of the 20th century.

More recent research is again reporting GC-induced stimulatory effects on a variety of inflammatory response components. These effects are usually observed at low GC concentrations, close to concentrations that are observed in vivo during basal, unstimulated states. For example, GC-mediated stimulation has been reported for the hepatic acute-phase response, for cytokine secretion, expression of cytokine/chemokine receptors, and for the pro-inflammatory mediator, macrophage migration inhibition factor. It seems clear that the long-held clinical view that GCs act solely as anti-inflammatory agents needs to be re-assessed. Varying doses of GCs do not lead simply to varying degrees of inflammation suppression, but rather GCs can exert a full range of effects from permissive to stimulatory to suppressive.

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