Stress and the inflammatory response: a review of neurogenic inflammation

Brain Behav Immun. 2002 Dec;16(6):622-53. doi: 10.1016/s0889-1591(02)00021-1.


The subject of neuroinflammation is reviewed. In response to psychological stress or certain physical stressors, an inflammatory process may occur by release of neuropeptides, especially Substance P (SP), or other inflammatory mediators, from sensory nerves and the activation of mast cells or other inflammatory cells. Central neuropeptides, particularly corticosteroid releasing factor (CRF), and perhaps SP as well, initiate a systemic stress response by activation of neuroendocrinological pathways such as the sympathetic nervous system, hypothalamic pituitary axis, and the renin angiotensin system, with the release of the stress hormones (i.e., catecholamines, corticosteroids, growth hormone, glucagons, and renin). These, together with cytokines induced by stress, initiate the acute phase response (APR) and the induction of acute phase proteins, essential mediators of inflammation. Central nervous system norepinephrine may also induce the APR perhaps by macrophage activation and cytokine release. The increase in lipids with stress may also be a factor in macrophage activation, as may lipopolysaccharide which, I postulate, induces cytokines from hepatic Kupffer cells, subsequent to an enhanced absorption from the gastrointestinal tract during psychologic stress. The brain may initiate or inhibit the inflammatory process. The inflammatory response is contained within the psychological stress response which evolved later. Moreover, the same neuropeptides (i.e., CRF and possibly SP as well) mediate both stress and inflammation. Cytokines evoked by either a stress or inflammatory response may utilize similar somatosensory pathways to signal the brain. Other instances whereby stress may induce inflammatory changes are reviewed. I postulate that repeated episodes of acute or chronic psychogenic stress may produce chronic inflammatory changes which may result in atherosclerosis in the arteries or chronic inflammatory changes in other organs as well.

Publication types

  • Review

MeSH terms

  • Acute-Phase Reaction / immunology
  • Animals
  • Humans
  • Hypothalamo-Hypophyseal System / immunology*
  • Neuritis / immunology*
  • Neuroimmunomodulation / immunology*
  • Stress, Physiological / immunology*