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.