IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors

• Published in: Neurobiology of disease 2006-09, Vol.23 (3), p.587-594
• Main Authors: Chourbaji, Sabine, Urani, Alexandre, Inta, Ioana, Sanchis-Segura, Carles, Brandwein, Christiane, Zink, Mathias, Schwaninger, Markus, Gass, Peter
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Anxiety; Anxiety Disorders - genetics; Anxiety Disorders - immunology; Anxiety Disorders - physiopathology; Behavior, Animal - physiology; Brain Chemistry - genetics; Brain Chemistry - immunology; Cytokines; Depression; Depressive Disorder - genetics; Depressive Disorder - immunology; Depressive Disorder - physiopathology; Disease Models, Animal; Genetic Predisposition to Disease - genetics; Helplessness, Learned; Hippocampus - immunology; Hippocampus - metabolism; Hippocampus - physiopathology; IL-6; Interleukin-6 - genetics; Interleukin-6 - immunology; Interleukin-6 - metabolism; Knockout mice; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction - genetics; Signal Transduction - immunology; Stress, Psychological - genetics; Stress, Psychological - immunology; Stress, Psychological - physiopathology
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2006.05.001

Cytokine-dependent mechanisms in the CNS have been implicated in the pathogenesis of depression. Interleukin-6 is upregulated in depressed patients and dowregulated by antidepressants. It is, however, unknown whether IL-6 is involved in the pathogenesis of depression. We subjected IL-6-deficient mice (IL-6 −/−) to depression-related tests (learned helplessness, forced swimming, tail suspension, sucrose preference). We also investigated IL-6 in the hippocampus of stressed wild-type mice. IL-6 −/− mice showed reduced despair in the forced swim, and tail suspension test, and enhanced hedonic behavior. Moreover, IL-6 −/− mice exhibited resistance to helplessness. This resistance may be caused by the lack of IL-6, because stress increased IL-6 expression in wild-type hippocampi. This suggests that IL-6 is a component in molecular mechanisms in the pathogenesis of depression. IL-6 −/− mice represent tools to study IL-6-dependent signaling pathways in the pathophysiology of depression in vivo. Moreover, these mice may support the screening of compounds for depression by altering cytokine-mediated signaling.