Further evidence for the depressive effects of cytokines: anhedonia and neurochemical changes.
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-1beta (IL-1beta), necrosis factor-alpha (TNF-alpha) and endotoxin challenge. Unlike IL-1beta, 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.
Anisman
Hymie
H
Institute of Neuroscience, Life Science Research Building, Carleton University, Ottawa, ON, Canada. hanisman@ccs.carleton.ca
Kokkinidis
Larry
L
Merali
Zul
Z
D000324:Adrenocorticotropic Hormone / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001007:Anxiety / Q000276:immunology; D001522:Behavior, Animal; D003072:Cognition Disorders / Q000276:immunology; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000276:immunology; D003863:Depression / Q000276:immunology*; D004298:Dopamine / Q000276:immunology; D004731:Endotoxins / Q000009:adverse effects; D006801:Humans; D007375:Interleukin-1 / Q000009:adverse effects; D007376:Interleukin-2 / Q000009:adverse effects*; D007858:Learning / Q000187:drug effects; D008569:Memory Disorders / Q000276:immunology; D019964:Mood Disorders / Q000276:immunology; D009638:Norepinephrine / Q000276:immunology; D012701:Serotonin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects
D004731:Endotoxins; D007375:Interleukin-1; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine; D009638:Norepinephrine