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THE EFFECTS OF PSYCHOLOGICAL STRESS ON HUMANS: INCREASED PRODUCTION OF PRO-INFLAMMATORY CYTOKINES AND Th1-LIKE RESPONSE IN STRESS-INDUCED ANXIETY
Abstract
There is some evidence that, in humans and experimental animals, psychological stress may suppress or enhance immune functions, depending on the nature of the stressor and the immune variables under consideration. The possibility that psychological stress may affect the production of pro-inflammatory and immunoregulatory cytokines was investigated in 38 medical students, who had blood samplings a few weeks before and after as well as one day before an academic examination. Psychological stress significantly increased the stimulated production of tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-1 receptor antagonist (IL-1Ra), interferon gamma (IFN-gamma) and IL-10. Students with high stress perception during the stressful condition had a significantly higher production of TNF-alpha, IL-6, IL-1Ra and IFN-gamma than students with a low-stress perception. Students with a high anxiety response had a significantly higher production of IFN-gamma and a lower production of the negative immunoregulatory cytokines, IL-10 and IL-4, than students without anxiety. These findings suggest that, in humans, changes in the production of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IFN-gamma, and negative immunoregulatory cytokines, IL-10 and IL-4, take part in the homeostatic responses to psychological stress and that stress-induced anxiety is related to a T-helper-1-like response.
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“Production of IL-6 and other proinflammatory cytokines can be directly stimulated by depression and other negative emotions and stressful experiences (16-20).”
From Chronic stress and age-related increases in the proinflammatory cytokine IL-6. (2003) · cites this paper as [19]
In the citing paper
“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 Maes et al., 1998
In the citing paper
“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 Maes et al., 1998
In the citing paper
“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 Maes et al., 1998
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“Either directly, or via the HPA-axis and the autonomous nervous system [31], the inflammation system is additionally activated by stress, evident by increased production of proinflammatory cytokines from immune cells and tissues, such as Il-6, TNF-α, and interferon-γ [32, 33].”
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“[215] M.”
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“Additionally, psychological stress — a known risk factor for depression — can trigger an in fl ammatory response involving these pro-in fl ammatory cytokines and is linked to the onset of depressive symptoms [29].”
Maes, M. H. J. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.023 · Cited by 98
“The mechanisms whereby psychological stress may precipitate or perpetuate ME/CFS are an increased production of pro-inflammatory cytokines (Maes et al., 1998); weakening of the antioxidant defenses, such as the glutathione antioxidant pathway (Goncalves et al., 2008); and induction of O&NS,…”
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“, 2001) and IL-6 (Brydon et al., 2005; Maes et al., 1998) levels.”
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“…shown that major psychiatric disorders including depression, anxiety, schizophrenia and Alzheimer’s disease as well as chronic stress perturb multiple biological pathways measurable in peripheral immune cells (Irwin, 1999; Maes et al., 1998, 1999b; Ohmori et al., 2005; Schwarz et al., 2001a,b).”
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“Long-term or severe fatigue may also increase the incidence of diseases related to the immune system [2], such as aging, multiple sclerosis, and Parkinson’s disease, which is seriously harmful to the work and life of patients [3].”
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“Moreover, high levels of TNF-alpha have been associated with symptoms of anxiety in humans under conditions of psychological stress 52 or following administration of LPS. 53 Interestingly, benzodiazepines have been shown to inhibit LPS-induced production of TNF-alpha from human microglial cells 54…”
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Metadata
- Authors
- Maes, M., Song, C., Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., Bosmans, E., De Meester, I., Benoy, I., Neels, H., Demedts, P., Janca, A., Scharpé, S., & Smith, R. S.
- Affiliations
- Vanderbilt University (US)
- Carleton University (CA)
- University of Antwerp (BE)
- Corresponding author
- Maes, Michael
- Venue
- Cytokine
- Publisher
- Elsevier BV
- Published
- 1998-04
- Volume
- 10
- Issue
- 4
- Pages
- 313-318
- ISSN
- 1043-4666 (ISSN-L)
- OpenAlex
- W2066503688
- Cited by
- 772
- References
- 0
- Citations by year
- 2026: 16 · 2025: 22 · 2024: 31 · 2023: 21 · 2022: 27 · 2021: 31 · 2020: 32 · 2019: 28 · 2018: 41 · 2017: 23 · 2016: 35 · 2015: 19 · 2014: 32 · 2013: 39 · 2012: 36
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
- Keywords
- psychological stress, stress-induced anxiety, inflammatory cytokines, TNF-α, interleukin-6, interferon-gamma, IL-10, IL-4, interleukin-1 receptor antagonist, perceived stress, immune function, medical students
- MeSH terms
- Adult, Anxiety, Female, Humans, Male, Stress, Physiological, Cytokines, Th1 Cells
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