Major Depression and Activationof the Inflammatory ResponseSystém

Overview

In the present paper, we propose a concise immune-activationmodel of depression. The hypothesis is based on the following findings. 1)There is now some evidence that there is activation of the inflammatoryresponse system (IRS) in major depression: increased numbers of leukocytes,monocytes, neutrophils, activated T-lymphocytes, and increased productionof interleukin-1 (IL-1), IL-2, IL-6 and interferon- (IFN). 2) There is evidencethat an acute phase response, with increased plasma concentrations of posi-tive acute phase proteins, occurs in depression. 3) IRS activation in depressi-on is related to and may explain neuroendocrine disorders occurring in thetillness, such as activation of the hypothalamic-pituitary-adrenal-axis and re-duced availability of plasma tryptophan, the precursor of serotonin. 4) Proin-flammatory cytokines given to humans or animals produce depressivesymptoms and depression. 5) Depression is a stress-induced disease: external(psychosocial stressors) and internal (organic stressors) stressors are empha-sised. Psychological stress in humans and experimental animals results inincreased production of proinflammatory cytokines, such as IL-6, IFN andTNF. Internal stressors, such as infections, stroke, autoimmune disordersand conditions, such as the postpartum period, are well established causes ofdepression and IRS activation. 6) Antidepressants, such as tricyclic antidep-ressants and selective serotonin reuptake inhibitors, suppress the producti-on of IL-6, IL-1b and IFN and increase the production of IL-10. This suggeststhat antidepressants have anti-inflammatory effects.

Key words:
depression, cytokines, inflammation, antidepressants, sero-tonin, cortisol.