Neuropsychiatric disorders related to interferon and interleukins treatment

Metab Brain Dis. 2009 Mar;24(1):55-68. doi: 10.1007/s11011-008-9114-5. Epub 2008 Dec 10.


Certain cytokines such as interferon-alpha and interleukin-2 are often used in the treatment certain cancers and chronic diseases such as melanoma, hepatitis C infection and multiple sclerosis. Several neuropsychiatric side effects such as depression, anxiety, psychosis, suicidal ideation, hypomanic mood and cognitive impairment were reported in those patients who received those medications. In certain patients with those neuropsychiatric side effects, the symptoms ceased when the medication was stopped. However, in some cases, the cognitive impairment persisted even for years after cessation of the medication. In animal studies, those cytokines could induce sickness behaviour, anxiety behaviour and social anhedonia. The increased in pro-inflammatory cytokines in certain neuropsychiatric disorders was widely reported. In addition, in animal studies, the treatment with interferon-alpha or interleukin-1 could induce depressive like behaviour. Recently, the role of certain pro-inflammatory cytokines that could enhance the activity of the enzyme, indoleamine 2-3, dioxygenase (IDO) which in turn would increase tryptophan degradation into kynurenine and decrease tryptophan availability of tryptophan in the brain to synthesize serotonin, a neurotransmitter which is necessary for the normal mood state became of interest in pathophysiology of psychiatric disorders. Furthermore, the imbalance in the further downward catabolic kynurenine pathway and their interactions with other neurotransmitters has been proposed to play an important role. The presence of such an imbalance in patients being treated with cytokines and in patients with psychiatric disorders and the possible consequence of those changes on the neuroprotective function in the brain are discussed in this review.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / immunology
  • Brain / physiopathology
  • Brain Diseases, Metabolic / chemically induced
  • Brain Diseases, Metabolic / immunology
  • Brain Diseases, Metabolic / physiopathology
  • Cytokines / adverse effects*
  • Cytokines / metabolism
  • Encephalitis / chemically induced*
  • Encephalitis / complications*
  • Encephalitis / physiopathology
  • Humans
  • Interferons / adverse effects
  • Interferons / metabolism
  • Interleukins / adverse effects
  • Interleukins / metabolism
  • Kynurenine / metabolism
  • Mental Disorders / chemically induced*
  • Mental Disorders / immunology
  • Mental Disorders / physiopathology
  • Tryptophan / metabolism


  • Cytokines
  • Interleukins
  • Kynurenine
  • Tryptophan
  • Interferons