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.
Integrity signals
Registry
Cites
Statistics
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?
Production of IL-6 and other proinflammatory cytokines can be directly stimulated by depression and other negative emotions and stressful experiences.
“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]
Psychological stress increases circulating levels of IL6 in humans and laboratory animals.
“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
Standard laboratory models of acute stress-including tube restraint, cage switching, and social isolation-induced high levels of circulating IL6.
“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
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.
“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
Cited by
Sorted by citations
Psychological stress and the human immune system: a meta-analytic study of 30 Years of inquiry
Segerstrom, S. C., & Miller, G. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.4.601 · Cited by 3,334 · see citing works
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009 · see citing works
“Weathering” and Age Patterns of Allostatic Load Scores Among Blacks and Whites in the United States
Geronimus, A. T., Hicken, M., Keene, D., & Bound, J. (2006) · American Journal of Public Health · doi:10.2105/ajph.2004.060749 · Cited by 2,525 · see citing works
The Bidirectional Relationship of Depression and Inflammation: Double Trouble
Beurel, E., Toups, M., & Nemeroff, C. B. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.002 · Cited by 2,136 · see citing works
“…psychological stress, a prominent risk factor for depression, induces an inflammatory response, and elevation of inflammatory markers after stress in healthy volunteers, including these proinflammatory cytokines, is associated with the development of depressive symptoms (Maes et al., 1998; Neuron.”
BackgroundGoldsmith, D. R., Rapaport, M. H., & Miller, B. J. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.3 · Cited by 1,683 · see citing works
A Systematic Review Assessing Bidirectionality between Sleep Disturbances, Anxiety, and Depression
Alvaro, P. K., Roberts, R. M., & Harris, J. K. (2013) · Sleep · doi:10.5665/sleep.2810 · Cited by 1,573 · see citing works
DS14: Standard Assessment of Negative Affectivity, Social Inhibition, and Type D Personality
Denollet, J. (2005) · Psychosomatic Medicine · doi:10.1097/01.psy.0000149256.81953.49 · Cited by 1,556 · see citing works
So depression is an inflammatory disease, but where does the inflammation come from?
Berk, M., Williams, L. J., Jacka, F. N., O’Neil, A., Pasco, J. A., Moylan, S., Allen, N. B., Stuart, A. L., Hayley, A. C., Byrne, M. L., et al. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-200 · Cited by 1,423 · see citing works
Self-citationChildhood maltreatment predicts adult inflammation in a life-course study
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610362104 · Cited by 1,264 · see citing works
Chronic stress and age-related increases in the proinflammatory cytokine IL-6.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1531903100 · Cited by 1,220 · see citing works
Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology.
Kiecolt-Glaser, J. K., McGuire, L., Robles, T. F., & Glaser, R. (2002) · Annual Review of Psychology · doi:10.1146/annurev.psych.53.100901.135217 · Cited by 1,176 · see citing works
“Emotions and Immune System Alterations There is excellent evidence that depression and anxiety enhance the production of proinflammatory cytokines, including IL-6 (Dentino et al. 1999; Lutgendorf et al. 1999; Maes et al. 1995, 1999, 1998).”
BackgroundMaes, M., Galecki, P., Chang, Y. S., & Berk, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.05.004 · Cited by 1,140 · see citing works
Self-citationCRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.
Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2013.06.004 · Cited by 972 · see citing works
Maes, M., Yirmyia, R., Noraberg, J., Brene, S., Hibbeln, J., Perini, G., Kubera, M., Bob, P., Lerer, B., & Maj, M. (2009) · Metabolic Brain Disease · doi:10.1007/s11011-008-9118-1 · Cited by 894 · see citing works
“Maes et al (1998a, 1998b) were the first to show that in humans psychological stress induces an inflammatory response with increased production of pro-inflammatory cytokines, such as IFNγ and TNFα.”
BackgroundSelf-citationCytokines and the Brain: Implications for Clinical Psychiatry
Kronfol, Z., & Remick, D. G. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.683 · Cited by 784 · see citing works
Immune Activation in Patients With Irritable Bowel Syndrome
Liebregts, T., Adam, B., Bredack, C., Röth, A., Heinzel, S., Lester, S., Downie–Doyle, S., Smith, E., Drew, P., Talley, N. J., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.01.046 · Cited by 660 · see citing works
Naldi, L., Chatenoud, L., Linder, D., Fortina, A. B., Peserico, A., Virgili, A., Bruni, P. L., Ingordo, V., Scocco, G. L., Solaroli, C., et al. (2005) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2005.23681.x · Cited by 642 · see citing works
Fillman, S. G., Cloonan, N., Catts, V. S., Miller, L. C., Wong, J., McCrossin, T., Cairns, M., & Weickert, C. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.110 · Cited by 609 · see citing works
Psychological stress in IBD: new insights into pathogenic and therapeutic implications
Mawdsley, J. E., & Rampton, D. S. (2005) · Gut · doi:10.1136/gut.2005.064261 · Cited by 622 · see citing works
Major Depression and Activation of The Inflammatory Response System
Maes, M. (1999) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-585-37970-8_2 · Cited by 617 · see citing works
Self-citationMaes, M. H. J., Kubera, M., & Leunis, J. (2008) · PubMed · Cited by 607 · see citing works
Self-citationNeuroimmune mechanisms of depression
Hodes, G. E., Kana, V., Menard, C., Merad, M., & Russo, S. J. (2015) · Nature Neuroscience · doi:10.1038/nn.4113 · Cited by 585 · see citing works
Systematic Review of Gut Microbiota and Major Depression
Cheung, S. G., Goldenthal, A. R., Uhlemann, A.-C., Mann, J. J., Miller, J. M., & Sublette, M. E. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00034 · Cited by 597 · see citing works
Depression and immune function
Kiecolt-Glaser, J. K., & Glaser, R. (2002) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00309-4 · Cited by 571 · see citing works
Depression and anxiety in patients with Inflammatory Bowel Disease: a systematic review
Neuendorf, R., Harding, A., Stello, N., Hanes, D., & Wahbeh, H. (2016) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2016.06.001 · Cited by 561 · see citing works
Maes, M. (2011) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.06.014 · Cited by 544 · see citing works
Self-citationNormal Responses to Injury Prevent Systemic Inflammation and Can Be Immunosuppressive
Munford, R. S., & Pugin, J. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.163.2.2007102 · Cited by 520 · see citing works
Critical role of nociceptor plasticity in chronic pain
Reichling, D. B., & Levine, J. D. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.07.007 · Cited by 495 · see citing works
The role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
“Psychological stress has been shown to reliably induce pro‐inflam‐ matory cytokine production in murine models (Bailey et al., 2011; Zhang et al., 2015) and in human subjects (Baumeister, Akhtar, Ciufolini, Pariante, & Mondelli, 2016; Maes et al., 1998; Wright et al., 2005).”
BackgroundZahalka, A. H., & Frenette, P. S. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0237-2 · Cited by 470 · see citing works
Maes, M. H. J., Christophe, A. B., Delanghe, J., Altamura, C. A., Neels, H. M., & Meltzer, H. Y. (1999) · Psychiatry Research · doi:10.1016/s0165-1781(99)00014-1 · Cited by 452 · see citing works
Self-citationInterleukin-1 (IL-1): A central regulator of stress responses
Goshen, I., & Yirmiya, R. (2009) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2008.10.001 · Cited by 399 · see citing works
Gut microbiome diversity is associated with sleep physiology in humans
Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., Parikh, E., Lopez, J. V., & Tartar, J. L. (2019) · PLOS ONE · doi:10.1371/journal.pone.0222394 · Cited by 390 · see citing works
Self-citationKiecolt‐Glaser, J. K., Bennett, J. M., Andridge, R., Peng, J., Shapiro, C. L., Malarkey, W. B., Emery, C. F., Layman, R. M., Mrózek, E., & Glaser, R. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.8860 · Cited by 392 · see citing works
Maes, M., Lin, A.-H., Delmeire, L., Van Gastel, A., Kenis, G., De Jongh, R., & Bosmans, E. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00131-0 · Cited by 387 · see citing works
Self-citationProinflammatory cytokines in the prefrontal cortex of teenage suicide victims
Pandey, G. N., Rizavi, H. S., Ren, X., Fareed, J., Hoppensteadt, D. A., Roberts, R. C., Conley, R. R., & Dwivedi, Y. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.08.006 · Cited by 378 · see citing works
“Also, a number of studies suggest that exposure to stressful life events causes impairment in various aspects of cellular immune function (Connor and Leonard, 1998; Maes et al., 1998).”
BackgroundPhysiological correlates of burnout among women
Grossi, G., Perski, A., Evengård, B., Blomkvist, V., & Orth-Gomér, K. (2003) · Journal of Psychosomatic Research · doi:10.1016/s0022-3999(02)00633-5 · Cited by 359 · see citing works
The Association of Depression and Anxiety with Pain: A Study from NESDA
de Heer, E. W., Gerrits, M. M. J. G., Beekman, A. T. F., Dekker, J., van Marwijk, H. W. J., de Waal, M. W. M., Spinhoven, P., Penninx, B. W. J. H., & van der Feltz-Cornelis, C. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106907 · Cited by 363 · see citing works
“However, another explanation might be possible as well; stress induced anxiety has an elevating effect on cytokines [49], and elevated cytokines lead to pain symptoms.”
BackgroundPsychoneuroimmunology and Psychosomatic Medicine: Back to the Future
Kiecolt‐Glaser, J. K., McGuire, L. M., Robles, T. F., & Glaser, R. (2002) · Psychosomatic Medicine · doi:10.1097/00006842-200201000-00004 · Cited by 359 · see citing works
Lymphocytes as a neural probe: potential for studying psychiatric disorders
Gladkevich, A. V., Kauffman, H. F., & Korf, J. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.01.009 · Cited by 359 · see citing works
Maes, M. H. J. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00088-8 · Cited by 357 · see citing works
Self-citationStress-Induced Changes in Skin Barrier Function in Healthy Women
Altemus, M. M., Rao, B. K., Dhabhar, F. S., Ding, W., & Granstein, R. D. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2001.01373.x · Cited by 347 · see citing works
Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder
Hoge, E. A., Brandstetter, K., Moshier, S., Pollack, M. H., Wong, K. K., & Simon, N. M. (2009) · Depression and Anxiety · doi:10.1002/da.20564 · Cited by 343 · see citing works
Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study
Wallace, D. J., Linker‐Israeli, M., Hallegua, D. S., Silverman, S. L., Silver, D., & Weisman, M. H. (2001) · Lara D. Veeken · doi:10.1093/rheumatology/40.7.743 · Cited by 334 · see citing works
Stress, age, and immune function: toward a lifespan approach
Graham, J. E., Christian, L. M., & Kiecolt-Glaser, J. K. (2006) · Journal of Behavioral Medicine · doi:10.1007/s10865-006-9057-4 · Cited by 329 · see citing works
“Related to wound healing, examination stress can alter the production of certain cytokines (Deinzer et al., 1999; Dobbin et al., 1991; Maes et al., 1998) that mediate inflammatory processes central to wound healing.”
BackgroundMcDade, T. W., Hawkley, L. C., & Cacioppo, J. T. (2006) · Psychosomatic Medicine · doi:10.1097/01.psy.0000221371.43607.64 · Cited by 326 · see citing works
The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6
Lin, A., Kenis, G., Bignotti, S., Tura, G. J. B., Jong, R. D., Bosmans, E., Pioli, R., Altamura, C. A., Scharpé, S., & Maes, M. H. J. (1998) · Schizophrenia Research · doi:10.1016/s0920-9964(98)00034-6 · Cited by 321 · see citing works
Self-citationSalim, S., Chugh, G., & Asghar, M. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00001-5 · Cited by 315 · see citing works
“Several groups have reported a positive correlation between anxiety and inflammatory markers in humans (TNFa, IL-6, and CRP) (Arranz et al., 2007; Maes et al., 1998; Pitsavos et al., 2006).”
Won, E., & Kim, Y.-K. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666151208113006 · Cited by 300 · see citing works
“Acute and chronic stressors have also been reported to affect the immune system, and an increase in various inflammatory markers has been reported in states of acute stress [13] and chronic stress [14].”
BackgroundOrigin and function of stress-induced IL-6 in murine models
Qing, H., Desrouleaux, R., Israni-Winger, K., Mineur, Y. S., Fogelman, N., Zhang, C., Rashed, S., Palm, N. W., Sinha, R., Picciotto, M. R., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.054 · Cited by 303 · see citing works
“…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).”
InfluentialO’Donovan, A., Hughes, B. M., Slavich, G. M., Lynch, L., Cronin, M.-T., O’Farrelly, C., & Malone, K. M. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.03.003 · Cited by 296 · see citing works
“Furthermore, the limited research on state anxiety and inflammation has yielded a mixed pattern of results (Chandrashekara et al., 2007; Maes et al., 1998).”
BackgroundKunz-Ebrecht, S., Mohamed‐Ali, V., Feldman, P. J., Kirschbaum, C., & Steptoe, A. (2003) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(03)00029-1 · Cited by 290 · see citing works
Acute inflammation and negative mood: mediation by cytokine activation
Wright, C. E., Strike, P. C., Brydon, L., & Steptoe, A. (2005) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2004.10.003 · Cited by 287 · see citing works
Miura, H., Ozaki, N., Sawada, M., Isobe, K., Ohta, T., & Nagatsu, T. (2008) · Stress · doi:10.1080/10253890701754068 · Cited by 282 · see citing works
“Psychological stress, specifically, an academic examination for medical students, significantly increases blood proinflammatory cytokines (Maes et al. 1998).”
BackgroundAcute mental stress elicits delayed increases in circulating inflammatory cytokine levels
STEPTOE, A., WILLEMSEN, G., OWEN, N., FLOWER, L., & MOHAMED-ALI, V. (2001) · Clinical Science · doi:10.1042/cs1010185 · Cited by 354 · see citing works
Anxiety in relation to inflammation and coagulation markers, among healthy adults: The ATTICA Study
Pitsavos, C., Panagiotakos, D. B., Papageorgiou, C., Tsetsekou, E., Soldatos, C., & Stefanadis, C. (2006) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.06.001 · Cited by 283 · see citing works
Zhao, X., Cao, F., Liu, Q., Li, X., Xu, G., Liu, G., Zhang, Y., Yang, X., Yi, S., Xu, F., et al. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.05.064 · Cited by 278 · see citing works
Stress as a neuroinflammatory condition in brain: Damaging and protective mechanisms
García‐Bueno, B., Caso, J. R., & Leza, J. C. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2008.04.001 · Cited by 280 · see citing works
Neuroinflammation, Neurodegeneration, and Depression
Hurley, L. L., & Tizabi, Y. (2012) · Neurotoxicity Research · doi:10.1007/s12640-012-9348-1 · Cited by 260 · see citing works
“Maes et al. (1998) were the first to show that psychological stress in humans induces an inflammatory response through production of pro-inflammatory cytokines, such as IFN-c and TNF-a.”
BackgroundEffect of inflammation, smoking and stress on gingival crevicular fluid cytokine level
Giannopoulou, C., Kamma, J. J., & Mombelli, A. (2003) · Journal Of Clinical Periodontology · doi:10.1034/j.1600-051x.2003.300201.x · Cited by 252 · see citing works
Salivary markers of inflammation in response to acute stress
Slavish, D. C., Graham‐Engeland, J. E., Smyth, J. M., & Engeland, C. G. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.08.008 · Cited by 263 · see citing works
“…acute stress and IL-4, although the human literature linking stress and other inflammatory cytokines is more robust (Steptoe et al., 2007); for example, anxiety induced by examination stress appears to reduce production of IL-4 and another antiinflammatory cytokine (IL-10) (Maes et al., 1998) .”
InfluentialE., O. I., McGaw, L. J., Naidoo, V., & Eloff, J. N. (2007) · AFRICAN JOURNAL OF BIOTECHNOLOGY · doi:10.5897/ajb2007.000-2457 · Cited by 248 · see citing works
Coussons‐Read, M. E., Lobel, M., Carey, J. C., Kreither, M., D'Anna‐Hernandez, K., Argys, L. M., Ross, R. G., Brandt, C., & Cole, S. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.02.009 · Cited by 245 · see citing works
Neeman, E., & Ben‐Eliyahu, S. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.03.006 · Cited by 245 · see citing works
“…stressors perturb immune indices, including cytokine levels and their induced production, number and distribution of leukocyte subtypes, and cellular and humoral immune functions (Ben-Eliyahu, 2003; Maes et al., 1998; Segerstrom and Miller, 2004; Stefanski, 2001; Viswanathan and Dhabhar, 2005).”
BackgroundImmunological effects of induced shame and guilt
Dickerson, S. S., Kemeny, M. E., Aziz, N., Kim, K. H., & Fahey, J. L. (2004) · Psychosomatic Medicine · doi:10.1097/01.psy.0000097338.75454.29 · Cited by 245 · see citing works
“Psychological stressors (ie, examinations, public speaking) can increase proinflammatory cytokine activity ( 18 , 19), suggesting that inflammatory processes could be sensitive to the emotions experienced in these circumstances.”
BackgroundPsychological Distress Impairs Clearance of Psoriasis in Patients Treated With Photochemotherapy
Fortune, D. G., Richards, H. L., Kirby, B., McElhone, K., Markham, T., Rogers, S., Main, C. J., & Griffiths, C. E. M. (2003) · Archives of Dermatology · doi:10.1001/archderm.139.6.752 · Cited by 244 · see citing works
Glaser, R., Robles, T. F., Sheridan, J. F., Malarkey, W. B., & Kiecolt‐Glaser, J. K. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.10.1009 · Cited by 242 · see citing works
Genetics of inflammation and risk of coronary artery disease: the central role of interleukin-6
Woods, A. (2000) · European Heart Journal · doi:10.1053/euhj.1999.2207 · Cited by 238 · see citing works
“Preliminary data suggest that humans also respond to stressful stimuli in the same way([72,73]).”
BackgroundSong, C., Lin, A., Bonaccorso, S., Heide, C., Verkerk, R., Kenis, G., Bosmans, E., Scharpe, S., Whelan, A., Cosyns, P., et al. (1998) · Journal of Affective Disorders · doi:10.1016/s0165-0327(98)00025-1 · Cited by 232 · see citing works
Self-citationMadrigal, J. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00292-5 · Cited by 232 · see citing works
“…evidence has shown that physical and psychological stress elevates plasma levels of several cytokines in animals and humans (i.e. TNF, IL-6, IFN ), the physiological significance of such elevation remains to be elucidated (Yamasu et al. 1992; Nukina et al. 1998; Maes et al. 1998; Dunn et al. 1999).”
BackgroundPsychological interactions with infertility among women
Cwikel, J., Gidron, Y., & Sheiner, E. (2004) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2004.05.004 · Cited by 225 · see citing works
Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia
Upthegrove, R., & Khandaker, G. M. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_88 · Cited by 230 · see citing works
Suarez, E. C., Krishnan, R. R., & Lewis, J. G. (2003) · Psychosomatic Medicine · doi:10.1097/01.psy.0000035719.79068.2b · Cited by 199 · see citing works
“BDI was not associated with either race (F(4,48) 1.”
BackgroundFineberg, A. M., & Ellman, L. M. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.01.001 · Cited by 200 · see citing works
Social integration and concentrations of C-reactive protein among US adults
Ford, E. S., Loucks, E. B., & Berkman, L. F. (2006) · Annals of Epidemiology · doi:10.1016/j.annepidem.2005.08.005 · Cited by 201 · see citing works
Peripheral Markers of Depression
Nobis, A., Zalewski, D., & Waszkiewicz, N. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9123793 · Cited by 197 · see citing works
“Psychological stressors induce cytokine production and an inflammatory response [162] which facilitates the generation of reactive oxygen and nitrogen species (ROS/RNS), leading to a pro-oxidant state.”
BackgroundLiebregts, T., Adam, B., Bredack, C., Gururatsakul, M., Pilkington, K. R., Brierley, S. M., Blackshaw, L. A., Gerken, G., Talley, N. J., & Holtmann, G. (2011) · The American Journal of Gastroenterology · doi:10.1038/ajg.2010.512 · Cited by 194 · see citing works
Genetic predictors of human chronic pain conditions
Zorina-Lichtenwalter, K., Meloto, C. B., Khoury, S., & Diatchenko, L. B. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.04.041 · Cited by 192 · see citing works
Caso, J. R., Pradillo, J. M., Hurtado, O., Leza, J. C., Moro, M. Á., & Lizasoaín, I. (2008) · Stroke · doi:10.1161/strokeaha.107.498212 · Cited by 193 · see citing works
“Several groups (n6 to 9 in each group) were used: (1) a control group (animals were handled for a few seconds once at 11 AM); ( 2 ) a subacute stress group (immobilization for 1 hour for 7 days) euthanized 24 hours after the last immobilization exposure (S7); (3) a permanent MCAO group euthanized 24 hours after operat…”
MethodHou, R., Garner, M., Holmes, C., Osmond, C., Teeling, J., Lau, L., & Baldwin, D. S. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.01.021 · Cited by 191 · see citing works
Goebel, M. U., Mills, P. J., Irwin, M. R., & Ziegler, M. G. (2000) · Psychosomatic Medicine · doi:10.1097/00006842-200007000-00019 · Cited by 189 · see citing works
Neuroimmunological effects of physical exercise in depression
Eyre, H. A., & Baune, B. T. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.09.015 · Cited by 188 · see citing works
Socioeconomic status and stress-induced increases in interleukin-6
Brydon, L., Edwards, S., Mohamed‐Ali, V., & Steptoe, A. (2003) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2003.09.011 · Cited by 189 · see citing works
Role of infection in irritable bowel syndrome
Spiller, R. C. (2007) · Journal of Gastroenterology · doi:10.1007/s00535-006-1925-8 · Cited by 187 · see citing works
van Dooren, F. E. P., Schram, M. T., Schalkwijk, C. G., Stehouwer, C. D. A., Henry, R. M. A., Dagnelie, P. C., Schaper, N. C., Kallen, C., Koster, A., Sep, S. J. S., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.03.004 · Cited by 187 · see citing works
Youssef, N. A., Abdelmalek, M. F., Binks, M., Guy, C. D., Omenetti, A., Smith, A. D., Diehl, A. M. E., & Suzuki, A. (2013) · Liver International · doi:10.1111/liv.12165 · Cited by 182 · see citing works
Moylan, S., Jacka, F. N., Pasco, J. A., & Berk, M. (2013) · Brain and Behavior · doi:10.1002/brb3.137 · Cited by 186 · see citing works
“For example, psychological stress has been associated with increased production of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and IFN-c, coupled with decreased production of anti-inflammatory cytokines including interleukin…”
BackgroundInfluentialReader, B. F., Jarrett, B. L., McKim, D. B., Wohleb, E. S., Godbout, J. P., & Sheridan, J. F. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.01.001 · Cited by 179 · see citing works
“…are not fully understood, the individual response to prolonged or severe stressors contributes to the development and exacerbation of depression and anxiety (Maes et al., 1998; Kalynchuk et al., 2004; Raison et al., 2006; Norman et al., 2010; Capuron and Miller, 2011; Gilman et al., 2013).”
BackgroundDiz-Chaves, Y., Astiz, M., Bellini, M. J., & García‐Segura, L. M. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.11.013 · Cited by 178 · see citing works
Maes, M. H. J. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(00)00094-3 · Cited by 179 · see citing works
Self-citationAssociation between −G308A tumor necrosis factor alpha gene polymorphism and schizophrenia
Boin, F., Zanardini, R., Pioli, R., Altamura, C. A., Maes, M. H. J., & Gennarelli, M. (2000) · Molecular Psychiatry · doi:10.1038/sj.mp.4000815 · Cited by 179 · see citing works
Self-citationNaldi, L., Peli, L., Parazzini, F., et al. (2001) · Journal of the American Academy of Dermatology · doi:10.1067/mjd.2001.110876 · Cited by 177 · see citing works
Inflammatory cytokines, socioeconomic status, and acute stress responsivity
Steptoe, A., Owen, N., Kunz-Ebrecht, S., & Mohamed‐Ali, V. (2002) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00030-2 · Cited by 176 · see citing works
Relation of social integration to inflammatory marker concentrations in men and women 70 to 79 years
Loucks, E. B., Berkman, L. F., Gruenewald, T. L., & Seeman, T. E. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.10.043 · Cited by 170 · see citing works
Conley, C. S., Travers, L. V., & Bryant, F. B. (2012) · Journal of American College Health · doi:10.1080/07448481.2012.754757 · Cited by 174 · see citing works
Stress, Allostatic Load, and Health of Mexican Immigrants<sup>*</sup>
Kaestner, R., Pearson, J. A., Keene, D., & Geronimus, A. T. (2009) · Social Science Quarterly · doi:10.1111/j.1540-6237.2009.00648.x · Cited by 171 · see citing works
“…environmental risk (Seeman et al. 2001; Uchino et al. 1996; Roy et al. 1998; Steptoe et al. 2002; Cohen et al. 1999; Marmot et al 1998; Daniel et al. 1999; Schnorpfiel et al. 2003;Weinstein et al. 2003; Wadhwa et al. 2001; Stancil et al. 2000; Maes et al. 1998; Evans 2003; Geronimus et al. 2007).”
BackgroundSong, C., Zhang, X., & Manku, M. S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3569-08.2009 · Cited by 169 · see citing works
“First, stress, as a trigger for depression, can increase inflammatory responses (Maes et al., 1998; Calcagni and Elenkov, 2006; Pace et al., 2007).”
BackgroundSelf-citationAhmad, S. F., Zoheir, K. M. A., Ansari, M. A., Nadeem, A., Bakheet, S. A., AL-Ayadhi, L. Y., Alzahrani, M. Z., Al-Shabanah, O. A., Al-Harbi, M. M., & Attia, S. M. (2017) · Molecular Neurobiology · doi:10.1007/s12035-016-9977-0 · Cited by 155 · see citing works
Honig, A., Kuyper, A. M. G., Schene, A. H., van Melle, J. P., de Jonge, P., Tulner, D. M., Schins, A., Crijns, H. J. G. M., Kuijpers, P. M. J. C., Vossen, H., et al. (2007) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31814b260d · Cited by 167 · see citing works
Denollet, J., Pedersen, S. S., Ong, A. T. L., Erdman, R. A. M., Serruys, P. W. J. C., & van Domburg, R. T. (2005) · European Heart Journal · doi:10.1093/eurheartj/ehi616 · Cited by 165 · see citing works
- 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
- Health Sciences › Medicine › Psychiatry and Mental health › 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
