Further evidence for the depressive effects of cytokines: Anhedonia and neurochemical changes

Hymie Anisman, Larry Kokkinidis, Zul Merali

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)


Although human studies have emphasized a role for IL-2 in depressive illness, limited attention has been devoted to the behavioral and neurochemical effects of this cytokine in animal studies. The present review assesses the behavioral effects of IL-2 in rodents, in counterpoint to the effects of interleukin-1β (IL-1β), necrosis factor-α (TNF-α) and endotoxin challenge. Unlike IL-1β, systemic IL-2 provokes modest effects on hypothalamic-pituitary-adrenal (HPA) functioning, and does not provoke marked signs of illness or anxiety. In some respects, however, IL-2 elicits effects reminiscent of traditional stressors, including anhedonia (diminished pleasure gained from otherwise rewarding stimuli). Additionally, when chronically administered, IL-2 may impact on cognitive processes, including spatial working memory. While IL-2 may induce depressive-like symptoms, the available data are sparse, have hardly considered the impact of chronic cytokine treatment, only assessed behavior in a narrow range of tests, and it remains to be established whether the effects of IL-2 are modifiable by antidepressant treatments. Finally, as the effects of IL-2 on CNS processes vary in a biphasic fashion, and may also engender neurotoxic effects, further analyses are necessary to discern under what conditions this cytokine provokes depressive-like behavioral outcomes.

Original languageEnglish
Pages (from-to)544-556
Number of pages13
JournalBrain, Behavior, and Immunity
Issue number5
Publication statusPublished - 2002
Externally publishedYes


  • Anxiety
  • Depression
  • Dopamine
  • Interleukin-1
  • Interleukin-2
  • Lipopolysaccharide
  • Norepinephrine
  • Serotonin


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