Stress and the Gastrointestinal Tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance

Am J Physiol Gastrointest Liver Physiol. 2001 Mar;280(3):G315-8. doi: 10.1152/ajpgi.2001.280.3.G315.


The stress response in a healthy organism is generally viewed as a warning and thus a protective reaction to a threat. However, the response may be deleterious if it is linked to an inflammatory stimulus or if it proceeds an inflammatory event. Prior stress enhances the response to an inflammatory stimulus by a mechanism that is independent of the release of hypothalamic corticotropin-releasing factor (CRF) or arginine vasopressin. Putative mechanisms include an increase in intestinal permeability as well as the release of the proinflammatory neuropeptide substance P. Stress may also reactivate previous inflammation when applied in conjunction with a small luminal stimulus. This reactivation involves increased permeability and requires the presence of T lymphocytes. Inflammatory mediators activate hypothalamic pathways, and a negative feedback loop, mediated by CRF release, has been proposed because animals with impaired hypothalamic CRF responses are more susceptible to inflammatory stimuli. Together, these experimental observations provide insights into the expression of inflammatory disorders in humans, including inflammatory bowel disease and postinfective irritable bowel syndrome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arginine Vasopressin / metabolism
  • Capillary Permeability / immunology
  • Colonic Diseases, Functional / etiology*
  • Colonic Diseases, Functional / immunology
  • Colonic Diseases, Functional / metabolism
  • Corticotropin-Releasing Hormone / metabolism
  • Humans
  • Inflammatory Bowel Diseases / etiology*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Mice
  • Rats
  • Stress, Physiological / complications*
  • Stress, Physiological / immunology
  • Stress, Physiological / metabolism
  • Substance P / metabolism


  • Arginine Vasopressin
  • Substance P
  • Corticotropin-Releasing Hormone