Administration of interferon-alpha in mice provokes peripheral and central modulation of immune cells, accompanied by behavioral effects.
BACKGROUND
Interferon-alpha (IFN-alpha) is used in the treatment of many viral and malignant diseases. Although IFN-alpha administration is highly efficacious, treatment is often complicated by psychiatric side effects such as depression, which may require discontinuation of the therapy. Unfortunately, the mechanisms underlying IFN-alpha-induced depression are still not well understood.


METHODS
In this study, we explored behavioral and immune effects of IFN-alpha administration in mice. BALB/c mice received daily intraperitoneal injections of 60,000 U/kg murine IFN-alpha for 8 days. Behavioral and immunological analysis was performed at least 15 h after injection to avoid any acute IFN-alpha effect. We monitored depression and anxiety-like behavior in mice using the Forced Swimming Test (FST), Tail Suspension Test (TST), and Elevated Plus Maze (EPM). Moreover, we studied the expression of adhesion molecules on peripheral blood leukocytes and analyzed the recruitment of lymphocyte subsets into the brain.


RESULTS
IFN-alpha administration resulted in increased immobility of mice in the late phase of FST, without significant effects in TST and EPM. Increased percentages of natural killer cells and lymphocytes expressing LFA-1 or Mac-1 were observed in peripheral blood. The percentages of CD4+ and CD8+ lymphocytes as well as the percentages of LFA-1-expressing CD4+ and CD8+ lymphocytes were increased in the brains of IFN-alpha-treated mice.


CONCLUSIONS
Our data suggest that IFN-alpha administration leads to an increase in peripheral blood cells with migratory potential, accompanied by an increased number of lymphocytes in brain, whilst the detectable modulation of the behavior was rather modest.
Orsal
Arif S
AS
Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitatsmedizin Berlin, Campus Mitte, Berlin, Germany. arif.oersal@charite.de
Blois
Sandra M
SM
Bermpohl
Daniela
D
Schaefer
Martin
M
Coquery
Nicolas
N
D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000139:chemically induced*; D004731:Endotoxins / Q000378:metabolism; D005434:Flow Cytometry; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D016207:Cytokines; D004731:Endotoxins; D016898:Interferon-alpha; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen