The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore

Trends Endocrinol Metab. 2013 Mar;24(3):109-19. doi: 10.1016/j.tem.2012.11.005. Epub 2013 Jan 8.

Abstract

Glucocorticoids are essential for maintaining homeostasis and regulate a wide variety of physiological processes. Therapeutically, synthetic glucocorticoids are widely prescribed for the treatment of inflammation, autoimmune disorders, and malignancies of lymphoid origin. In this review we examine emerging evidence highlighting both proinflammatory and anti-inflammatory actions of glucocorticoids on both the innate and adaptive immune systems. We incorporate these findings into the more traditional anti-inflammatory role attributed to glucocorticoids, and propose how the two seemingly disparate processes seamlessly work together to resolve cellular responses to inflammatory stimuli. These ideas provide a framework by which glucocorticoids ready and reinforce the innate immune system, and repress the adaptive immune system, to help to resolve inflammation and restore homeostasis.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Anti-Inflammatory Agents / therapeutic use
  • Glucocorticoids / physiology
  • Glucocorticoids / therapeutic use*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Immunity, Innate / drug effects
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation Mediators / physiology
  • Pituitary-Adrenal System / drug effects
  • Receptors, Glucocorticoid / physiology
  • Signal Transduction / drug effects
  • Transcription Factors / antagonists & inhibitors

Substances

  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Inflammation Mediators
  • Receptors, Glucocorticoid
  • Transcription Factors