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Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10
Open accessAbstract
Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST) is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.
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“Further, prolonged restraint stress decreases anti-inflammatory IL-4 and IL-10 [176].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [176]
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“In the periphery, chronically stressed mice upregulate the pro-inflammatory cytokine interleukin 6 (IL-6) [175–177].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [176]
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“Parallel to clinical studies, rodents exposed to stressors (e.g., restraint, footshock and social defeat stress) have increased circulating IL-6 [14–17].”
From Interleukin-6 Induced by Social Stress Promotes a Unique Transcriptional Signature in the Monocytes That Facilitate Anxiety (2019) · cites this paper as [14]
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Metadata
- Authors
- Voorhees, J. L., Tarr, A. J., Wohleb, E. S., Godbout, J. P., Mo, X., Sheridan, J. F., Eubank, T. D., & Marsh, C. B.
- Affiliations
- The Ohio State University (US)
- Corresponding author
- Eubank, Timothy D.
- Marsh, Clay B.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-03-08
- Volume
- 8
- Issue
- 3
- Pages
- e58488
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3592793
- OpenAlex
- W2044404835
- Cited by
- 236
- References
- 87
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 19 · 2023: 14 · 2022: 20 · 2021: 19 · 2020: 19 · 2019: 22 · 2018: 22 · 2017: 21 · 2016: 18 · 2015: 22 · 2014: 12 · 2013: 9
- FWCI
- 6.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH-R01, UL1TR000090, T32 HL07946)
- National Heart, Lung, and Blood Institute (R01HL067176, T32HL007946, R01HL102464, T32 HL07946)
- National Cancer Institute (P30CA016058)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- restraint stress, chronic stress, depression, interleukin-6, IL-10, inflammatory cytokines, depression-like behavior, recombinant IL-10, hippocampus, cortex, major depressive disorder, antidepressant mechanism
- MeSH terms
- Animals, Behavior, Animal, Depression, Immobilization, Recombinant Proteins, Stress, Physiological, Time Factors, Interleukin-6, Interleukin-10, Mice
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