Pegylated human interferon alpha 2a does not induce depression-associated changes in mice.
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.
Kosel
Markus
M
Psychiatric University Hospital, University of Bonn, Bonn, Germany.
Bilkei-Gorzo
Andras
A
Zawatzky
Rainer
R
Zimmer
Andreas
A
Schlaepfer
Thomas E
TE
D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects*; D003863:Depression / Q000139:chemically induced*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011994:Recombinant Proteins; D013997:Time Factors
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a