IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors
Open accessAbstract
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.
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Leukocyte-derived sources of IL-6 may be critical in mediating these behavioral effects.
“suggests that leukocyte-derived sources of IL-6 may be critical in mediating these behavioral effects (34).”
From Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress (2014) · cites this paper as [34]
IL-6 is sufficient to induce depressive-like behavior in rodent models.
“is sufficient to induce depressive-like behavior in rodent models”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [5]
IL-6 is elevated in the serum of a subset of depressed patients.
“the inflammatory cytokine interleukin-6 (IL-6) is elevated in the serum of a subset of depressed patients”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [5]
Deletion of the IL-6 gene is protective against depressive-like behavior in rodent models.
“whereas deletion of the IL-6 gene is protective (3–5, 8)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [5]
IL-6 is activated in conditions associated with depression in humans and in rodent models.
“is activated in conditions associated with depression in humans and in rodent models”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [5]
Immune system actions profoundly impact mood regulation.
“a growing recognition that immune system actions profoundly impact mood regulation (3–6)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [5]
IL-6KO mice are resilient to learned helplessness behavior in response to uncontrollable foot-shocks, forced swim, and tail suspension.
“Notably, IL-6KO mice were resilient to learned helplessness behavior in response to uncontrollable foot-shocks, forced swim, and tail suspension [19].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [19]
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References 53 · Cited by 241
- Authors
- Chourbaji, S., Urani, A., Inta, I., Sanchis-Segura, C., Brandwein, C., Zink, M., Schwaninger, M., & Gass, P.
- Affiliations
- Central Institute of Mental Health (DE)
- Heidelberg University (DE)
- Corresponding author
- Chourbaji, Sabine
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 23
- Issue
- 3
- Pages
- 587-594
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W1984877838
- Cited by
- 241
- References
- 53
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 13 · 2022: 13 · 2021: 24 · 2020: 14 · 2019: 18 · 2018: 8 · 2017: 8 · 2016: 17 · 2015: 17 · 2014: 26 · 2013: 9 · 2012: 11
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- interleukin-6, depression, IL-6 knockout mice, stress-induced depression, learned helplessness, forced swim test, tail suspension test, sucrose preference, hippocampus, cytokines, antidepressant resistance, hedonic behavior, depression pathogenesis
- MeSH terms
- Animals, Anxiety Disorders, Behavior, Animal, Brain Chemistry, Depressive Disorder, Disease Models, Animal, Helplessness, Learned, Hippocampus, Mice, Inbred C57BL, Stress, Psychological, Signal Transduction, Interleukin-6, Mice, Knockout, Genetic Predisposition to Disease, Mice
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