The DOI matches its Crossref record.
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Citations
Cited by
Sorted by citations
Items 701–772 of 772
Maes, M. H. J., Kenis, G., Kubera, M., et al. (2003)
Self-citationNeuroendocrine and cytokines-induced responses to minutes, hours, and days of mental stress.
Matalka, K. Z. (2003) · PubMed · Cited by 44
POSSIBLE ROLE OF CYTOKINES IN FIBROMYALGIA
Saad, H. F., & Yassien, M. M. (2003)
Chrysanthou‐Piterou, M., Kloukina, I., Havaki, S., Liappas, J., & Issidorides, M. R. (2014) · PubMed
Extracellular adenosine as a novel neuroimmune modulator
Chiu, G. S. (2014) · Illinois Digital Environment for Access to Learning and Scholarship (University of Illinois at Urbana-Champaign)
Crowe, M. A. (2004) · Research Exchange (Washington State University)
Alvaro, P. K. (2014) · Adelaide Research & Scholarship (AR&S) (University of Adelaide)
The Effect of Cooling the Head to Reduce Brain Temperature on Stress
Knox, A. M. (2013) · UC Research Repository (University of Canterbury) · doi:10.26021/6622
Prolil oligopeptidases de tripanossomos : aspectos estruturais e funcionais
Motta, F. N. (2010)
Gjerstad, A. C. (2011) · NORA - Norwegian Open Research Archives
Heart rate variability in animal models of psychological-cardiovascular comorbidity
Trombini, M. (2012) · DSpaceUnipr (University of Parma)
Immunopathology of the Nervous System
Remick, A. K., Pershing, M. L., Papenfuss, T. L., Lanigan, L. G., Beck, M. J., & Toot, J. (2017) · Molecular and integrative toxicology · doi:10.1007/978-3-319-47385-7_5 · Cited by 1
Psychosocial Stress and Addison's Disease
Wolf, J. M. (2006)
Modulation of oxidative stress and inflammation using a grape seed derived polyphenol
Petersen-Ross, K. S. (2016) · SUNScholar (Stellenbosch University)
The impact of social stress on acute Theiler's murine encephalitis virus infection.
Johnson, R. R. (2004) · OakTrust (Texas A&M University Libraries)
Unemployment and health in the UK: Exploring psychobiological pathways
Hughes, A. (2016) · UCL Discovery (University College London)
The Impact of Stress and Inflammatory Processes on Cognitive Change in Late Adulthood
Balasubramanian, A. B. (2010) · eScholarship (California Digital Library)
Qi, C., Ma, X. Z., Chen, H. C., Wang, Q. J., Gao, L., Yin, J., & Jing, Y. (2018) · Neuropsychiatry · doi:10.4172/neuropsychiatry.1000376
Testing a model predicting depression, anxiety and stress in parents of children with Down syndrome
Hek, J. V. D. (2018) · UTAS Research Repository · doi:10.25959/23238215
Bennett, C. M. (2018) · Journal of International Crisis and Risk Communication Research
Chronic stress and ageing : effects on immune function
Vitlić, A. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Stress, Inflammation and Cancer Prognosis: New Evidence-Based Effective Treatments
Gidron, Y., Caton, L., & Reich, M. (2019) · Psycho-Oncologie · doi:10.3166/pson-2019-0101
Lee, H., Oh, J. H., Um, Y. H., Kim, S., Kim, T., Seo, H., Hong, S., & Jeong, J. (2020) · Mood and Emotion · doi:10.35986/me.2020.18.1.9
Hotwater Extract of Rhus Verniciflua Stokes Improves Exercise Performance in Mice
Kim, M., Na, C.-S., Choon, Y. Y., et al. (2014) · Yakhak Hoeji
Watling, S. E. (2019) · TSpace (University of Toronto)
Marqueurs biochimiques de la dépression : actualité et perspectives
Guillotin, S., Yrondi, A., & Delcourt, N. (2021) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(21)00195-7 · Cited by 1
The Stressful Life of the Urban Consumers: The Case of Dhaka City Residents
Masoom, M. R. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.747414
“There is some evidence that the degree of psychological and biological responses to stress is influenced by the impression of control over stressful circumstances (Maes et al., 1998).”
BackgroundHochfeld, W. E. (2010) · UpSpace Institutional Repository (University of Pretoria)
Cytokines and Stressors: Implications for Cancer Immunotherapy
Kusnecov, A. W., & Anisman, H. (2010) · Springer eBooks · doi:10.1007/978-90-481-3725-1_1
Is inflammation related to self-rated health and mortality in men?
Warnoff, C. (2009) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Gandarela, L. M. (2021) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2021.tde-08122021-140003
Faculty Opinions recommendation of Origin and Function of Stress-Induced IL-6 in Murine Models.
Lynch, L. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738227474.793583818
Gidron, Y. (2020) · Springer eBooks · doi:10.1007/978-3-030-39903-0_1383
Gidron, Y. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6439-6_1383-2
(2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811351-6.00026-7
Apostolopoulos, N. C. (2018) · Springer eBooks · doi:10.1007/978-3-319-96800-1_7
Koenig, H. G. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811282-3.00007-0 · Cited by 1
The impact of type II diabetes on behavioral and cellular aspects of neuroplasticity
Georgescu, T. (2007) · Carleton University's Institutional Repository (MacOdrum Library, Carleton University) · doi:10.22215/etd/2007-08067
Wang, Y., Kim, S. H., Klein, M. E., Chen, J., Gu, E., Smith, S. B., Bortsov, A. V., Slade, G. D., Zhang, X., & Nackley, A. G. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.18.520949
Poincaré Plot Method for Physiological Analysis of the Gadget Use Effect on Children Stress Level
Zaky, U., Anggara, A., Zakariyah, M., & Fathullah, I. (2022) · Jurnal Online Informatika · doi:10.15575/join.v7i1.809
“Acute and chronic stress have also been reported to affect the immune system, and increase various inflammatory markers [40, 41].”
BackgroundOsman, B., Teesson, M., Marx, W., Thornton, L. K., Jacka, F. N., Hunter, E., Visontay, R., & Sunderland, M. (2023) · doi:10.31219/osf.io/ut584
Tooth loss in young mice is associated with cognitive decline and femur-bone mineral density
Hatakeyama, R., Oue, H., Yokoi, M., Ishida, E., & Tsuga, K. (2024) · Odontology · doi:10.1007/s10266-024-01008-x
(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.09996-8
Anisman, H., Hayley, S. P., & Kusnecov, A. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.00007-7
Mitra, S., Mitra, M., Nandi, D. K., et al. (2025) · Human Nutrition & Metabolism · doi:10.1016/j.hnm.2025.200323
RetractedASSOCIATION BETWEEN CHRONIC STRESS AND THE INTENSITY AND RECURRENCE OF PSORIATIC SYMPTOMS
Basak, A. E., Strużek, K., Kwiatkowska, A., Mączka, E., Tracz, W., Świercz, P., Teper, K., Khiralla-Gawlik, S., & Strzelecka, A. A. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(47).2025.3669
Seo, S., & Cortiñas, M. B. (2025) · Clinical Rheumatology · doi:10.1007/s10067-025-07859-1
Psychosocial Factors Affecting Pregnant Hispanic Women
Silveira, M. L. (2020) · ScholarWorks@UMassAmherst (University of Massachusetts Amherst) · doi:10.7275/y69m-cz51
van Vuuren, M. J. (2011) · SUNScholar (Stellenbosch University)
Phenotypic characterization of stress Leukocytosis
Anane, H. L. (2011) · University of Birmingham Institutional Research Archive (University of Birmingham)
Additional file 1 of HMGB1 in the mPFC governs comorbid anxiety in neuropathic pain
Du, Y., 徐层林, Yu, J., Liu, K., Lin, S.-D., Hu, T.-T., Qu, F.-H., Guo, F., Lou, G.-D., Nishibori, M., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20501971
KLF7 induced ADRB3-dependent IL-6 production in brown adipocytes during stress
Liang, M., Zhang, M., Hou, Y., Yuan, F., 张惠子, Zhao, M., Xu, L., Liu, Q., Su, Y., Chu, X., et al. (2026) · Journal of Lipid Research · doi:10.1016/j.jlr.2026.100981
“Numerous studies have confirmed that acute stress induces the release of IL-6 in human, rat, and mouse models (19 – 21); however, the origin of IL-6 and its correlation with organismal metabolism during acute stress remain unclear.”
Stress, Well-Being, and Reproduction in Wildlife
Edwards, K. L., Brown, J. L., Edes, A. N., & Hunt, K. E. (2026) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-87707-0_3 · Cited by 1
Orita, Y., Iwakawa, T., & Takeuchi, K. (2026) · Maternal Health Neonatology and Perinatology · doi:10.1186/s40748-026-00255-w
“In fact, psychologic stress was reported to increase pro-inflammatory cytokines such as TNF-α, IL-6, and interferon (IFN)-γ [14].”
Nur, T. A., Munny, F. A., Qusar, M. S., Islam, M. R., & Nahar, Z. (2026) · Developmental Neurobiology · doi:10.1002/dneu.70025
Communication in the Depressed Brain
Sunzeri, F. (2026) · Springer eBooks · doi:10.1007/978-3-032-14465-2_7
Effect of Medication Intake on Dental Implant‐Related Outcomes—A Scoping Review
Monje, A., Soldini, M. C., Couso‐Queiruga, E., Babiano, Á., & Chappuis, V. (2026) · Clinical Oral Implants Research · doi:10.1111/clr.70151 · Cited by 1
“These effects, combined with SSRI-induced modulation of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), may create a local pro-inflammatory environment that predisposes to peri-implant bone loss (Maes et al. 1998).”
Endocannabinoidsystem, Stress und psychische Gesundheit
O’Brien, K., & Blair, P. (2026) · Springer eBooks · doi:10.1007/978-3-032-14521-5_3
Rashid, M. H. B., Islam, M., Islam, S. M. A., & Islam, M. R. (2026) · Experimental Biology and Medicine · doi:10.3389/ebm.2026.11144
“These findings from preclinical studies can be further extrapolated to clinical studies, which have reported significantly higher levels of pro-inflammatory cytokines in GAD patients alongside lower anti-inflammatory cytokines when compared with healthy individuals [1, 17–23].”
Touw, D. C. W., Messaoudi, S. E., Mulder, W. J. M., Netea, M. G., Slavich, G. M., & Riksen, N. P. (2026) · FEBS Letters · doi:10.1002/1873-3468.70447
Liu, Q., Zhao, X., Zhu, X., Hu, J., Hu, G., Wang, Y., Yu, X., Sun, Z., Zhang, M., Liu, R., et al. (2026) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2026.108005
The Impact of Mental Challenge on Indicators of Endothelial Function in Obese Individuals
Huang, C.-J. (2009) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/jbvj-q998
Efeito de leucotrienos sobre o estado de ativação de macrófagos de camundongos estressados
Nunes, G. A. (2005) · Americanae (AECID Library)
Portugal, B. (2014) · Americanae (AECID Library)
Rating well-being and distress
Rafanelli, C., Park, S. K., Ruini, C., Ottolini, F., Cazzaro, M., & Fava, G. A. (2000) · Stress Medicine · doi:10.1002/(sici)1099-1700(200001)16:1
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review