Cytokines as a precipitant of depressive illness: Animal and human studies

Hymie Anisman, Zul Merali, Michael O. Poulter, Shawn Hayley

Research output: Contribution to journalReview articlepeer-review

184 Citations (Scopus)


Cytokines whose primary function is that of acting as signaling molecules of the immune system, have been implicated in the provocation or exacerbation of mood disorders such as depression. This position has been supported by several lines of evidence; (1) proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment. Interleukin-2 (IL-2) induces less profound sickness, but elicits anhedonia, a key symptom of depression; (2) neuroendocrine and central neurotransmitter changes, reminiscent of those implicated in depression, may be elicited by some of these cytokines, and these effects are exacerbated by stressors; (3) severe depressive illness is accompanied by elevations of cytokine production or levels, although these effects are not necessarily attenuated with antidepressant medication; and (4) immunotherapy, using IL-2 or IFN-α, promote depressive symptoms that are attenuated by antidepressant treatment. It is proposed that chronic cytokine elevations engender neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Further, the effects of the cytokine treatments may act synergistically with stressors, and cytokines may provoke a sensitization effect so that the effects of later stressor experiences are exacerbated.

Original languageEnglish
Pages (from-to)963-972
Number of pages10
JournalCurrent Pharmaceutical Design
Issue number8
Publication statusPublished - 2005
Externally publishedYes


  • Corticotropin releasing hormone
  • Cortisol
  • Cytokines
  • Depression
  • Dopamine
  • Hypothalamic-pituitary-adrenal axis
  • Interleukin
  • Norepinephrine
  • Serotonin


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