Abstract
Major depression is accompanied by various direct and indirect
indicators of a moderate activation of the inflammatory response
system (IRS). Increased production of proinflammatory cytokines,
such as interleukin-1 (IL-1), IL-6 and interferon (IFNg), may
play a crucial role in the immune and acute phase response in
depression. Lower serum zinc and changes in the erythron are
indirect indicators of IRS activation in depression. The reciprocal
relationships between IRS activation and hypothalamic-pituitary-adrenal
(HPA)-axis hyperactivity, alterations in HP thyroid (HPT)-axis
function and the availability of tryptophan to the brain led
us to hypothesize that these neuroendocrine changes in depression
are indicators of IRS activation and that a combined dysregulation
of the IRS, the turnover of serotonin (5-HT) and the HPA-axis
is an integral component of depression. The IRS activation model
of depression provides an explanation for the psycho-social
(external stress) as well as organic (internal stress) etiology
of major depression. Antidepressive treatments with various
antidepressive agents, including SSRIs, tricyclic and heterocyclic
antidepressants, have in vivo and in vitro negative immunoregulatory
effects, suggesting that their antidepressant efficacy may be
attributed, in part, to their immune effects.
