Decreased Interleukin-4 Release from the Neurons of the Locus Coeruleus in Response to Immobilization Stress
Open accessAbstract
It has been demonstrated that immobilization (IMO) stress affects neuroimmune systems followed by alterations of physiology and behavior. Interleukin-4 (IL-4), an anti-inflammatory cytokine, is known to regulate inflammation caused by immune challenge but the effect of IMO on modulation of IL-4 expression in the brain has not been assessed yet. Here, it was demonstrated that IL-4 was produced by noradrenergic neurons in the locus coeruleus (LC) of the brain and release of IL-4 was reduced in response to IMO. It was observed that IMO groups were more anxious than nontreated groups. Acute IMO (2 h/day, once) stimulated secretion of plasma corticosterone and tyrosine hydroxylase (TH) in the LC whereas these increments were diminished in exposure to chronic stress (2 h/day, 21 consecutive days). Glucocorticoid receptor (GR), TH, and IL-4-expressing cells were localized in identical neurons of the LC, indicating that hypothalamic-pituitary-adrenal- (HPA-) axis and sympathetic-adrenal-medullary- (SAM-) axis might be involved in IL-4 secretion in the stress response. Accordingly, it was concluded that stress-induced decline of IL-4 concentration from LC neurons may be related to anxiety-like behavior and an inverse relationship exists between IL-4 secretion and HPA/SAM-axes activation.
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Hippocampal IL4 levels vary inversely with stress vulnerability.
“Our results, together with evidence from the literature (26, 27), suggest that levels of hippocampal IL4 vary inversely with stress vulnerability.”
From IL4-driven microglia modulate stress resilience through BDNF-dependent neurogenesis (2021) · cites this paper as [27]
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- Authors
- Lee, H.-J., Park, H.-J., Starkweather, A., An, K., & Shim, I.
- Affiliations
- Kyung Hee University (KR)
- Virginia Commonwealth University (US)
- Corresponding author
- Shim, Insop
- Venue
- Mediators of Inflammation
- Publisher
- Wiley
- Published
- 2016
- Volume
- 2016
- Pages
- 1-8
- ISSN
- 0962-9351 (ISSN-L)
- 1466-1861
- PMC
- PMC4745346
- OpenAlex
- W2288061336
- Cited by
- 30
- References
- 57
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 1
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Mediators of Inflammation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VCU Scholars Compass (Virginia Commonwealth University) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Education, Science and Technology (2006-2005240, 2013R1A2A2A03069127)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- IL-4, locus coeruleus, restraint stress, neuroimmune interactions, noradrenergic neurons, anxiety-like behavior, corticosterone, tyrosine hydroxylase, glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, chronic stress, anti-inflammatory cytokines
- MeSH terms
- Animals, Enzyme-Linked Immunosorbent Assay, Locus Coeruleus, Male, Neurons, Random Allocation, Stress, Physiological, Interleukin-4, Rats, Sprague-Dawley, Maze Learning, Rats
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