Pegylated human interferon alpha 2a does not induce depression-associated changes in mice

Markus Kosel, Andras Bilkei-Gorzo, Rainer Zawatzky, Andreas Zimmer, Thomas E. Schlaepfer

Research output: Contribution to journalArticlepeer-review

Abstract

Interferon (IFN) alpha proteins are proinflammatory cytokines having immunomodulating and antiviral properties. States during which cytokine systems are activated (e.g., during viral infection or during treatment of chronic hepatitis C and various malignancies with IFN alpha, etc.) can be associated with depression-like syndromes or even full-blown depressive episodes. Therefore, the role of IFN alpha and other cytokines in the pathogenesis of depressive disorder ("cytokine hypothesis of depression") has been assessed for many years with contradictory results. We have investigated whether intraperitoneal administration of high doses (up to 600. μg/kg body weight) of pegylated, recombinant human IFN alpha 2a in mice induces changes known to be associated with depression using three different readouts: behavior in a model of despair (Porsolt swim test), presence of anhedonia (sucrose preference test), and sensitivity of the hypothalamic-pituitary-adrenal system (dexamethasone suppression test). We also assessed potential IFN-induced changes in gene expression in the liver. In none of the performed experiments, depression-associated effects could be found despite very high serum levels of IFN-induced antiviral activity compared to levels measured in hepatitis C virus (HCV) patients treated routinely with pegylated recombinant human IFN alpha 2a. The lack of such expected effects is probably due to the fact that pegylated human recombinant IFN alpha 2a does not activate the murine class I IFN receptor. Our results do not support the hypothesis that administration of recombinant pegylated human IFN alpha to mice produces a robust model of depression.

Original languageEnglish (US)
Pages (from-to)243-247
Number of pages5
JournalPsychiatry research
Volume185
Issue number1-2
DOIs
StatePublished - Jan 30 2011

Keywords

  • Anhedonia
  • Dexamethasone suppression test
  • Forced swim test
  • Pharmacokinetics

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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