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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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“Proinflammatory cytokines have been shown to increase in response to stress (a predictor of depressive episodes), be present at higher concentrations amongst MDD patients relative to controls, and be at higher baseline levels amongst non-responders to antidepressant therapy (Eller et al., 2008; Hiles et al., 2012; Ken…”
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“…diminished glucocorticoid binding affinity, thus decelerating HPA deactivation in response to stressors, as glucocorticoid receptor activity is needed for negative feedback on the HPA axis (Maes et al. 1998; Baker et al. 1999; Denny et al. 2000; Simeon et al. 2007; Binder et al. 2008; Binder 2009).”
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Neuroinflammation and Neurotransmission Mechanisms Involved in Neuropsychiatric Disorders
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Bülbüller, N., Kırkıl, C., Gödekmerdan, A., et al. (2013) · Indian Journal of Surgery · doi:10.1007/s12262-012-0796-x · Cited by 16
“In these patients, psychological stress which occurred in operating room can also induce the production of IL-6 because there were clinical and experimental evidences that psychological stressor elevates plasma IL-6 [19–21].”
BackgroundMarazziti, D., Ambrogi, F., Abelli, M., Nasso, E. D., Catena, M., Massimetti, G., Carlini, M., & Dell’Osso, L. (2007) · Stress · doi:10.1080/10253890601170563 · Cited by 16
“…of the most investigated conditions is students undertaking examinations, which is the subject of the majority of the studies reporting activation of lymphocytes, increase in NK and CD8þ lymphocytes and decreased CD4þ/CD8þ ratio (Brosschot et al. 1994; Benschop et al. 1995; Maes et al. 1998, 1999).”
BackgroundStress, immunité et physiologie du système nerveux
Jacque, C., & Thurin, J.-M. (2002) · médecine/sciences · doi:10.1051/medsci/200218111160 · Cited by 17
The Cytokine, Chemokine, and Growth Factor Network of Prenatal Depression
Maes, M. H. J., Abe, Y., Sirichokchatchawan, W., Suwimonteerabutr, J., Sangkomkamhangd, U., Almulla, A. F., & Satthapisit, S. (2023) · Brain Sciences · doi:10.3390/brainsci13050727 · Cited by 17
“In addition, Maes et al. [40] revealed that pregnant women with a history of major depression had elevated levels of IL-6 and soluble IL-1 receptor antagonist (sIL-1RA), suggesting sensitization of the immune-inflammatory response.”
BackgroundInfluentialSelf-citationHereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response
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Lucas, K., & Maes, M. H. J. (2013) · PubMed · doi:10.26187/deakin.33284208 · Cited by 14
Self-citationIssues in the Design and Implementation of Psychoneuroimmunology Research
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“Pertinent to this, stress is a major risk factor for MDD, and inflammation is a frequent response to stress (Maes et al., 1998; Miller and Raison, 2015, 2016).”
BackgroundMcDade, T. W., & Hayward, M. D. (2009) · Biodemography and Social Biology · doi:10.1080/19485560903382478 · Cited by 13
“Psychosocial stressors and symptoms of depression have been associated with increased production of proinflammatory cytokines and C-reactive protein (CRP; Maes et al. 1998 ; Dentino et al.”
BackgroundInflammation Through a Psychoneuroimmunological Lens
Bennett, J. M., Gillie, B. L., Lindgren, M. E., Fagundes, C. P., & Kiecolt-Glaser, J. K. (2013) · Handbook of Systems and Complexity in Health · doi:10.1007/978-1-4614-4998-0_19 · Cited by 15
Restraint stress induces and exacerbates intestinal inflammation in interleukin-10 deficient mice
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Anxiety and Extraversion in Lupus-Related Atherosclerosis
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“The results of meta-analysis studies showed that pro-inflammatory cytokines, such as IL-6 and TNF-α, have an important role in the molecular mechanism of depression- and anxiety-like behaviors (19, 29).”
Background
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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