title: Interferon-alpha effects are exaggerated when administered on a psychosocial stressor backdrop: cytokine, corticosterone and brain monoamine variations.
abstract: Immunotherapy involving interferon-alpha (IFN-alpha) treatment is often accompanied by symptoms of depressive illness. These effects may stem from the direct actions of the cytokine, or may be unique to individuals undergoing considerable strain. In two experiments using CD-1 mice, we demonstrate that intraperitoneal administration of IFN-alpha dose dependently influences plasma corticosterone and sickness behaviors, and modestly influences norepinephrine turnover in brain. However, when mice are exposed to a psychosocial stressor (social disruption by transferring mice from isolated to grouped conditions, and to a moderate extent a transfer from grouped housing to isolation), the effects of IFN-alpha on sickness, plasma corticosterone and hippocampal norepinephrine, as well as on the levels of circulating IL-6, TNF-alpha and IL-10 (but not IL-1beta or IFN-gamma) are greatly augmented. It is suggested that the depressive effects of immunotherapy in humans likewise reflects the synergistic actions of the cytokine and the ongoing distress experienced by patients.
authors.affiliation: Institute of Neuroscience, Carleton University, Ontario, Canada K1S 5B6. hanisman@ccs.carleton.ca
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.forename: Michael O
authors.initials: MO
authors.lastname: Poulter
authors.forename: Reno
authors.initials: R
authors.lastname: Gandhi
authors.forename: Zul
authors.initials: Z
authors.lastname: Merali
authors.forename: Shawn
authors.initials: S
authors.lastname: Hayley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000008:administration & dosage*; D016898:Interferon-alpha / Q000008:administration & dosage*; D051379:Mice; D011863:Radioimmunoassay / Q000379:methods; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: D015306:Biogenic Monoamines; D016207:Cytokines; D007155:Immunologic Factors; D016898:Interferon-alpha; D003345:Corticosterone