A pre-conditioning stress accelerates increases in mouse plasma inflammatory cytokines induced by stress
Open accessAbstract
BACKGROUND: Major depressive disorder is a prevalent disease that is inadequately treated with currently available interventions. Stress increases susceptibility to depression in patients and rodent models. Depression is also associated with aberrant activation of inflammation, such as increases in circulating levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNFα). The two main goals of this study were (i) to identify cytokine changes measuring a broad panel of 19 cytokines, and (ii) to test if a pre-conditioning stress altered the inflammatory response to a subsequent stress. RESULT: Stress-induced changes in mouse plasma cytokines were measured by multiplex following administration of one or two daily stresses of inescapable foot shocks using the learned helplessness paradigm for modeling depression-like behavior. Administration of inescapable foot shocks increased plasma levels of IL-1β, IL-6, TNFα, IL-3, IL-10, IL-13, IL-17A, IL-5, GM-CSF, IL-12(p70), IFN-γ, MIP-1α, MIP-1β, IL-1α, IL-2, KC, RANTES and G-CSF, with peak levels occurring in the range of 6 to 12 hr after stress. Pre-conditioning the mice 24 hr before with an equivalent inescapable foot shock stress resulted in similar magnitudes of increases in most cytokines as occurred after a single stress, but accelerated the increase, causing the levels of most cytokines to peak 1 hr after stress. These results demonstrate that a single stress induces the expression of many cytokines, and that sequential, daily stresses accelerates the rate of cytokine production. CONCLUSIONS: Acute stress broadly activates inflammation in mice, and the inflammatory response is more rapid following repeated stress, actions that may contribute to deleterious effects of stress on depression and other stress-linked diseases.
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Psychological stress increases circulating levels of IL6 in humans and laboratory animals.
“Studies dating back to 1990 have shown that psychological stress increase circulating levels of IL6 in humans and laboratory animals (Cheng et al., 2015; LeMay et al., 1990; Maes et al., 1998).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Cheng et al., 2015
Standard laboratory models of acute stress-including tube restraint, cage switching, and social isolation-induced high levels of circulating IL6.
“We found that standard laboratory models of acute stress—including tube restraint, cage switching, and social isolation—induced high levels of circulating IL6 (Figure 1A), consistent with previous studies demonstrating that stress alone induced IL6 (Cheng et al., 2015; LeMay et al., 1990; Maes et al., 1998).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Cheng et al., 2015
Psychological stress has been known to induce endocrine IL6 for nearly 30 years and has been shown in multiple species, including rats, mice, and humans.
“Psychological stress has been known to induce endocrine IL6 for nearly 30 years and has been shown in multiple species, including rats, mice, and humans (Cheng et al., 2015; LeMay et al., 1990; Maes et al., 1998).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Cheng et al., 2015
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Origin and function of stress-induced IL-6 in murine models
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- Authors
- Cheng, Y., Jope, R. S., & Beurel, E.
- Affiliations
- University of Miami (US)
- Corresponding author
- Jope, Richard S
- ORCID
- Cheng, Yuyan
- Venue
- BMC Neuroscience
- Published
- 2015-05-07
- Volume
- 16
- Issue
- 1
- Pages
- 31-31
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC4425917
- OpenAlex
- W1514423159
- Cited by
- 70
- References
- 53
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 9 · 2023: 10 · 2022: 5 · 2021: 14 · 2020: 5 · 2019: 8 · 2018: 8 · 2017: 3 · 2015: 1
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (K99MH090236, R00MH090236, MH090236, R56MH038752, MH038752, MH095380, R01MH038752, R01MH095380)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- inflammatory cytokines, plasma cytokines, major depressive disorder, learned helplessness, inescapable footshock, repeated stress, acute stress, IL-1β, interleukin-6, TNF-α, neuroinflammation, depression-like behavior
- MeSH terms
- Animals, Electroshock, Foot, Helplessness, Learned, Male, Mice, Inbred C57BL, Stress, Psychological, Time Factors, Cytokines
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