Suppression of cell proliferation by interferon-alpha through interleukin-1 production in adult rat dentate gyrus

Neuropsychopharmacology. 2006 Dec;31(12):2619-26. doi: 10.1038/sj.npp.1301137. Epub 2006 Jul 5.


The therapeutic use of interferon-alpha (IFN-alpha), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30-45% of patients, frequently interrupting treatment. IFN-alpha-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-alpha remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-alpha treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-alpha for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1beta), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-alpha. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-alpha-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-alpha suppresses neurogenesis in the DG, and that IL-1beta plays an essential role in the suppression. The decreased cell proliferation caused by IFN-alpha-induced IL-1beta may be responsible, at least in part, for IFN-alpha-induced depression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bromodeoxyuridine
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cell Proliferation / drug effects*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / immunology
  • Dentate Gyrus / physiopathology
  • Depressive Disorder / chemically induced
  • Depressive Disorder / immunology
  • Depressive Disorder / physiopathology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Immunologic Factors / adverse effects
  • Interferon-alpha / adverse effects*
  • Interleukin 1 Receptor Antagonist Protein / pharmacology
  • Interleukin-1beta / agonists*
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Male
  • Neurons / drug effects*
  • Neurons / immunology
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / immunology


  • Immunologic Factors
  • Interferon-alpha
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1
  • Bromodeoxyuridine