Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression

Med Hypotheses. 2003 Nov-Dec;61(5-6):519-25. doi: 10.1016/s0306-9877(03)00207-x.


There are different theories and hypotheses related to the aetiology of depression. The interaction between brain 5-HT level and the activity of its autoreceptors plays a role in mood changes and depression. In major depression, activation of the inflammatory response system (IRS) and, increased concentrations of proinflammatory cytokines, prostaglandin E2 and negative immuno-regulatory cytokines in peripheral blood have been reported. Recently, pro-inflammatory cytokines have been found to have profound effects on the metabolism of brain serotonin through the enzyme indoleamine-2,3-dioxygenase (IDO) that metabolizes the tryptophan, the precursor of 5-HT to neurodegenerative quinolinate and neuroprotective kynurenate. The cytokine-serotonin interaction that leads to the challenge between quinolinate and kynurenate in the brain explains the neurodegeneration hypothesis of depression.

MeSH terms

  • Cytokines / metabolism*
  • Depression / diagnosis*
  • Depression / etiology
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Kynurenic Acid / metabolism
  • Models, Biological
  • Models, Theoretical
  • Neurodegenerative Diseases / pathology*
  • Neurons / pathology
  • Protein Binding
  • Serotonin / metabolism*
  • Tryptophan / metabolism
  • Tryptophan Oxygenase / metabolism


  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Serotonin
  • Tryptophan
  • Tryptophan Oxygenase
  • Kynurenic Acid