Cited by 30Stress Responses and CortisolTryptophan and brain disordersNeuropeptides and Animal Physiology

Decreased Interleukin-4 Release from the Neurons of the Locus Coeruleus in Response to Immobilization Stress

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Lee, Hyun-ju, Park, Hyun-Jung, Starkweather, Angela, An, Kyungeh, Shim, Insop·2016·Mediators of Inflammation

Abstract

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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  1. [56]Zigmond M. J. Finlay J. M. Sved A. F. Friedman M. J. Charney D. S. Deutch A. Y. Neurochemical studies of central noradrenergic responses to acute and chronic stress—implications for normal and abnormal behavior Neurobiological and Clinical Consequences of Stress—From Normal Adaptation to Post-Traumatic Stress Disorder 1995 chapter 3 Philadelphia, Pa, USA Lippincott-Raven Publishers 45 60

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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
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
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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