Abstract
Folk wisdom has long suggested that stressful events take a toll on health. The field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence about the ways in which stressors — and the negative emotions that they generate — can be translated into physiological changes. PNI researchers have used animal and human models to learn how the immune system communicates bidirectionally with the central nervous and endocrine systems and how these interactions impact on health.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Psychosocial factors and patient and healthcare delays in large (class T3–T4) oral, oropharyngeal, and laryngeal carcinomas
BMC Cancer Open Access 25 June 2024
-
Social Media Posts from Friends during Late Adolescence as Predictors of Young Adult Physical Health
Journal of Youth and Adolescence Open Access 29 January 2024
-
Repressed Blautia-acetate immunological axis underlies breast cancer progression promoted by chronic stress
Nature Communications Open Access 03 October 2023
Access options
Subscribe to this journal
Receive 12 print issues and online access
195,33 € per year
only 16,28 € per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Rabin, B. S. Stress, Immune Function, and Health: the Connection (Wiley–Liss & Sons, New York, 1999).
Ader, R., Felten, D. L. & Cohen, N. (eds) Psychoneuroimmunology 3rd edn (Academic, San Diego, 2001).
Black, P. H. The inflammatory response is an integral part of the stress response: implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Brain Behav. Immun. 17, 350–364 (2003).
Cohen, S., Tyrrell, D. A. & Smith, A. P. Psychological stress and susceptibility to the common cold. N. Engl. J. Med. 325, 606–612 (1991).
Segerstrom, S. C. & Miller, G. E. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol. Bull. 130, 1–37 (2004).
Webster, J. I., Tonelli, L. & Sternberg, E. M. Neuroendocrine regulation of immunity. Annu. Rev. Immunol. 20, 125–163 (2002).
Padgett, D. A. & Glaser, R. How stress influences the immune response. Trends Immunol. 24, 444–448 (2003).
Weigent, D. A. & Blalock, J. E. Production of peptide hormones and neurotransmitters by the immune system. Chem. Immunol. 69, 1–30 (1997).
Bellinger, D. L., Lorton, D., Lubahn, C. & Felten, D. L. in Psychoneuroimmunology 3rd edn Vol. 2 (eds Ader, R., Felten, D. L. & Cohen, N.) 55–112 (Academic, San Diego, 2001).
Capuron, L., Ravaud, A., Miller, A. H. & Dantzer, R. Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-α cancer therapy. Brain Behav. Immun. 18, 205–213 (2004).
Maier, S. F. Bi-directional immune–brain communication: implications for understanding stress, pain, and cognition. Brain Behav. Immun. 17, 69–85 (2003).
Konstantinos, A. P. & Sheridan, J. F. Stress and influenza viral infection: modulation of proinflammatory cytokine responses in the lung. Respir. Physiol. 128, 71–77 (2001).
Bonneau, R. H., Padgett, D. A. & Sheridan, J. F. in Psychoneuroimmunology 3rd edn Vol. 2 (eds Ader, R., Felten, D. L. & Cohen, N.) 483–498 (Academic, San Diego, 2001).
Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B. & Sheridan, J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc. Natl Acad. Sci. USA 93, 3043–3047 (1996).
Vedhara, K. et al. Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 353, 627–631 (1999).
Deng, Y., Jing, Y., Campbell, A. E. & Gravenstein, S. Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly. J. Immunol. 172, 3437–3446 (2004).
Miller, G. E. et al. Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? Psychosom. Med. 66, 215–223 (2004).
Glaser, R. et al. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom. Med. 54, 22–29 (1992).
Morag, M., Morag, A., Reichenberg, A., Lerer, B. & Yirmiya, R. Psychological variables as predictors of rubella antibody titers and fatigue — a prospective, double blind study. J. Psychiatr. Res. 33, 389–395 (1999).
Glaser, R., Sheridan, J. F., Malarkey, W. B., MacCallum, R. C. & Kiecolt-Glaser, J. K. Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine. Psychosom. Med. 62, 804–807 (2000).
Burns, V. E., Drayson, M., Ring, C. & Carroll, D. Perceived stress and psychological well-being are associated with antibody status after meningitis C conjugate vaccination. Psychosom. Med. 64, 963–970 (2002).
Plotkin, S. A. Immunologic correlates of protection induced by vaccination. Pediatr. Infect. Dis. 20, 73–75 (2001).
Cohen, S. et al. Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol. 17, 214–223 (1998).
Stone, A. A. et al. Development of common cold symptoms following experimental rhinovirus infection is related to prior stressful life events. Behav. Med. 18, 115–120 (1992).
Leserman, J. et al. Progression to AIDS: the effects of stress, depressive symptoms, and social support. Psychosom. Med. 61, 397–406 (1999).
Cole, S. W., Kemeny, M. E., Taylor, S. E., Visscher, B. R. & Fahey, J. L. Accelerated course of human immunodeficiency virus infection in gay men who conceal their homosexual identity. Psychosom. Med. 58, 1–13 (1996).
Kasl, S. V., Evans, A. S. & Niederman, J. C. Psychosocial risk factors in the development of infectious mononucleosis. Psychosom. Med. 41, 445–466 (1979).
Cohen, F. et al. Persistent stress as a predictor of genital herpes recurrence. Arch. Intern. Med. 159, 2430–2436 (1999).
Luborsky, L., Mintz, J., Brightman, U. J. & Katcher, A. H. Herpes simplex and moods: a longitudinal study. J. Psychosom. Res. 20, 543–548 (1976).
Goldmeier, D. & Johnson, A. Does psychiatric illness affect the recurrence rate of genital herpes? Br. J. Vener. Dis. 58, 40–43 (1982).
Schmader, K., Studenski, S., MacMillan, J., Grufferman, S. & Cohen, H. J. Are stressful life events risk factors for herpes zoster? J. Am. Geriatr. Soc. 38, 1188–1194 (1990).
Payne, D. A., Mehta, S. K., Tyring, S. K., Stowe, R. P. & Pierson, D. L. Incidence of Epstein–Barr virus in astronaut saliva during spaceflight. Aviat. Space Environ. Med. 70, 1211–1213 (1999).
Mehta, S. K., Stowe, R. P., Feiveson, A. H., Tyring, S. K. & Pierson, D. L. Reactivation and shedding of cytomegalovirus in astronauts during spaceflight. J. Infect. Dis. 182, 1761–1764 (2000).
Prosch, S. et al. A novel link between stress and human cytomegalovirus (HCMV) infection: sympathetic hyperactivity stimulates HCMV activation. Virology 272, 357–365 (2000).
Sarid, O., Anson, O., Yaari, A. & Margalith, M. Epstein–Barr virus specific salivary antibodies as related to stress caused by examinations. J. Med. Virol. 64, 149–156 (2001).
Capitanio, J. P., Mendoza, S. P., Lerche, N. W. & Mason, W. A. Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome. Proc. Natl Acad. Sci. USA 95, 4714–4719 (1998).
Kusnecov, A. V. et al. Decreased herpes simplex viral immunity and enhanced pathogenesis following stressor administration in mice. J. Neuroimmunol. 38, 129–137 (1992).
Wonnacott, K. M. & Bonneau, R. H. The effects of stress on memory cytotoxic T lymphocyte-mediated protection against herpes simplex virus infection at mucosal sites. Brain Behav. Immun. 16, 104–117 (2002).
Cao, L., Martin, A., Polakos, N. & Moynihan, J. A. Stress causes a further decrease in immunity to herpes simplex virus-1 in immunocompromised hosts. J. Neuroimmunol. 156, 21–30 (2004).
Bonneau, R., Sheridan, J., Feng, N. & Glaser, R. Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms. J. Neuroimmunol. 42, 167–176 (1993).
Leo, N. A. & Bonneau, R. H. Mechanisms underlying chemical sympathectomy-induced suppression of herpes simplex virus-specific cytotoxic T lymphocyte activation and function. J. Neuroimmunol. 110, 45–56 (2000).
Halford, W. P., Gebhardt, B. M. & Carr, D. J. Mechanisms of herpes simplex virus type 1 reactivation. J. Virol. 70, 5051–5060 (1996).
Padgett, D. A. et al. Social stress and the reactivation of latent herpes simplex virus type 1. Proc. Natl Acad. Sci. USA 95, 7231–7235 (1998).
Irwin, M. R., Pike, J. L., Cole, J. C. & Oxman, M. N. Effects of a behavioral intervention, tai chi chih, on varicella-zoster virus specific immunity and health functioning in older adults. Psychosom. Med. 65, 824–830 (2003).
Glaser, R. et al. Stress-associated changes in the steady state expression of latent Epstein–Barr Virus: implications for chronic fatigue syndrome and cancer. Brain Behav. Immun. 19, 91–103 (2005).
Glaser, R., Kutz, L. A. & Malarkey, W. B. Hormonal modulation of Epstein–Barr virus replication. Neuroendocrinology 62, 356–361 (1995).
Glaser, R. et al. The differential impact of training stress and final examination stress on herpesvirus latency at the United States Military Academy at West Point. Brain Behav. Immun. 13, 240–251 (1999).
Hübner, G. et al. Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoid-treated mice. Cytokine 8, 548–556 (1996).
Werner, S. & Grose, R. Regulation of wound healing by growth factors and cytokines. Physiol. Rev. 83, 835–870 (2003).
Kiecolt-Glaser, J. K., Marucha, P. T., Malarkey, W. B., Mercado, A. M. & Glaser, R. Slowing of wound healing by psychological stress. Lancet 346, 1194–1196 (1995).
Marucha, P. T., Kiecolt-Glaser, J. K. & Favagehi, M. Mucosal wound healing is impaired by examination stress. Psychosom. Med. 60, 362–365 (1998).
Padgett, D. A., Marucha, P. T. & Sheridan, J. F. Restraint stress slows cutaneous wound healing in mice. Brain Behav. Immun. 12, 64–73 (1998).
DeRijk, R. et al. Exercise and circadian rhythm-induced variations in plasma cortisol differentially regulate interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) production in humans: high sensitivity of TNF-α and resistance of IL-6. J. Clin. Endocrinol. Metab. 82, 2182–2192 (1997).
Glaser, R. et al. Stress-related changes in proinflammatory cytokine production in wounds. Arch. Gen. Psychiatry 56, 450–456 (1999).
Follin, P. Skin chamber technique for study of in vivo exudated human neutrophils. J. Immunol. Methods 232, 55–65 (1999).
Contrada, R. J., Leventhal, E. A. & Anderson, J. R. in International Review of Health Psychology Vol. 3 (eds Maes, S., Leventhal, H. & Johnston, M.) 219–266 (Wiley & Sons, Chichester, 1994).
Kiecolt-Glaser, J. K., Page, G. G., Marucha, P. T., MacCallum, R. C. & Glaser, R. Psychological influences on surgical recovery: perspectives from psychoneuroimmunology. Am. Psychol. 53, 1209–1218 (1998).
Black, P. H. Stress and the inflammatory response: a review of neurogenic inflammation. Brain Behav. Immun. 16, 622–653 (2002).
Zhou, D., Kusnecov, A. W., Shurin, M. R., DePaoli, M. & Rabin, B. S. Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic–pituitary–adrenal axis. Endocrinology 133, 2523–2530 (1993).
Penninx, B. W. et al. Inflammatory markers and depressed mood in older persons: results from the health, aging, and body composition study. Biol. Psychiatry 54, 566–572 (2003).
Glaser, R., Robles, T., Sheridan, J., Malarkey, W. B. & Kiecolt-Glaser, J. K. Mild depressive symptoms are associated with amplified and prolonged inflammatory responses following influenza vaccination in older adults. Arch. Gen. Psychiatry 60, 1009–1014 (2003).
Maes, M., Ombelet, W., De Jongh, R., Kenis, G. & Bosmans, E. The inflammatory response following delivery is amplified in women who previously suffered from major depression, suggesting that major depression is accompanied by a sensitization of the inflammatory response system. J. Affect. Disord. 63, 85–92 (2001).
Johnson, J. D. et al. Prior stressor exposure sensitizes LPS-induced cytokine production. Brain Behav. Immun. 16, 461–476 (2002).
Harris, T. et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am. J. Med. 106, 506–512 (1999).
Kiecolt-Glaser, J. K. et al. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc. Natl Acad. Sci. USA 100, 9090–9095 (2003).
Epel, E. S. et al. Accelerated telomere shortening in response to life stress. Proc. Natl Acad. Sci. USA 101, 17312–17315 (2004).
Schulz, R. & Beach, S. R. Caregiving as a risk factor for mortality: the caregiver health effects study. JAMA 282, 2215–2219 (1999).
Marx, J. Inflammation and cancer: the link grows stronger. Science 306, 966–968 (2004).
Reiche, E. M. V., Nunes, S. O. V. & Morimoto, H. K. Stress, depression, the immune system, and cancer. Lancet Oncol. 5, 617–625 (2004).
Coe, C. L. & Lubach, G. R. Critical periods of special health relevance for psychoneuroimmunology. Brain Behav. Immun. 17, 3–12 (2003).
Antoni, M. H. et al. Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men. J. Consult. Clin. Psychol. 68, 31–45 (2000).
Fawzy, F. I. et al. Malignant melanoma: effects of an early structured psychiatric intervention, coping, and affective state on recurrence and survival 6 years later. Arch. Gen. Psychiatry 50, 681–689 (1993).
Kiecolt-Glaser, J. K. et al. Psychosocial enhancement of immunocompetence in a geriatric population. Health Psychol. 4, 25–41 (1985).
Andersen, B. L. et al. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. J. Clin. Oncol. 22, 3570–3580 (2004).
Bonneau, R. H., Sheridan, J. F., Feng, N. & Glaser, R. Stress-induced suppression of herpes simplex virus (HSV)-specific cytotoxic T lymphocyte and natural killer cell activity and enhancement of acute pathogenesis following local HSV infection. Brain Behav. Immun. 5, 170–192 (1991).
Johnson, R. R., Storts, R., Welsh T. H. Jr, Welsh, C. J. & Meagher, M. W. Social stress alters the severity of acute Theiler's virus infection. J. Neuroimmunol. 148, 74–85 (2004).
Sieve, A. N. et al. Chronic restraint stress during early Theiler's virus infection exacerbates the subsequent demyelinating disease in SJL mice. J. Neuroimmunol. 155, 103–118 (2004).
Cao, L., Hudson, C. A. & Lawrence, D. A. Acute cold/restraint stress inhibits host resistance to Listeria monocytogenes via β1-adrenergic receptors. Brain Behav. Immun. 17, 121–133 (2003).
Cao, L., Filipov, N. M. & Lawrence, D. A. Sympathetic nervous system plays a major role in acute cold/restraint stress inhibition of host resistance to Listeria monocytogenes. J. Neuroimmunol. 125, 94–102 (2002).
Campbell, T. et al. Neuropathogenesis of Theiler's virus infection: I. Acute disease. Brain Behav. Immun. 15, 235–254 (2001).
Mehta, S. K., Pierson, D. L., Cooley, H., Dubow, R. & Lugg, D. Epstein–Barr virus reactivation associated with diminished cell-mediated immunity in Antarctic expeditioners. J. Med. Virol. 61, 235–240 (2000).
Ironson, G. et al. Posttraumatic stress symptoms, intrusive thoughts, loss and immune function after Hurricane Andrew. Psychosom. Med. 59, 128–141 (1997).
Delahanty, D. L., Dougall, A. L. & Baum, A. in Psychoneuroimmunology 3rd edn Vol. 2 (eds Ader, R., Felten, D. L. & Cohen, N.) 335–348 (Academic, San Diego, 2001).
Lundberg, U. & Frankenhaeuser, M. Stress and workload of men and women in high-ranking positions. J. Occup. Health Psychol. 4, 142–151 (1999).
Dhabhar, F. S. Stress, leukocyte trafficking, and the augmentation of skin immune function. Ann. NY Acad. Sci. 992, 1–13 (2003).
Altemus, M., Rao, B., Dhabhar, F. S., Ding, W. & Granstein, R. D. Stress-induced changes in skin barrier function in healthy women. J. Invest. Dermatol. 117, 309–317 (2001).
Miller, A. H. et al. Glucocorticoid receptors are differentially expressed in the cells and tissues of the immune system. Cell. Immunol. 186, 45–54 (1998).
Elenkov, I. J. & Chrousos, G. P. Stress hormones, proinflammatory and anti-inflammatory cytokines, and autoimmunity. Ann. NY Acad. Sci. 966, 290–303 (2002).
Lai, J. P., Douglas, S. D. & Ho, W. Z. Human lymphocytes express substance P and its receptor. J. Neuroimmunol. 86, 80–86 (1998).
Petitto, J. M., Huang, Z. & McCarthy, D. B. Molecular cloning of NPY-Y1 receptor cDNA from rat splenic lymphocytes: evidence of low levels of mRNA expression and 125I-NPY binding sites. J. Neuroimmunol. 54, 81–86 (1994).
Radulovic, M., Dautzenberg, F. M., Sydow, S., Radulovic, J. & Spiess, J. Corticotropin-releasing factor receptor 1 in mouse spleen: expression after immune stimulation and identification of receptor-bearing cells. J. Immunol. 162, 3013–3021 (1999).
Clevenger, C. V., Freier, D. O. & Kline, J. B. Prolactin receptor signal transduction in cells of the immune system. J. Endocrinol. 157, 187–197 (1998).
Sun, R., Li, A. L., Wei, H. M. & Tian, Z. G. Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines. Cell Res. 14, 67–73 (2004).
Welniak, L. A., Sun, R. & Murphy, W. J. The role of growth hormone in T-cell development and reconstitution. J. Leukoc. Biol. 71, 381–387 (2002).
Sanders, V. M., Kasprowicz, D. J., Kohm, A. P. & Swanson, M. A. in Psychoneuroimmunology 3rd edn Vol. 1 (eds Ader, R., Felten, D. L. & Cohen, N.) 132–158 (Academic, San Diego, 2001).
Cloez-Tayarani, I., Petit-Bertron, A. -F., Venters, H. D. & Cavaillon, J. -M. Differential effect of serotonin on cytokine production in lipopolysaccharide-stimulated human peripheral blood mononuclear cells: involvement of 5–hydroxytryptamine 2A receptors. Int. Immunol. 15, 233–240 (2003).
Acknowledgements
We thank J. Sheridan, D. Padgett, R. Bonneau, R. Nelson, N. Quan and V. Sanders for helpful suggestions. Work on this paper was supported, in part, by grants from the General Clinical Research Center (Columbus, United States) and the Comprehensive Cancer Center, (Columbus, United States).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Glaser, R., Kiecolt-Glaser, J. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5, 243–251 (2005). https://doi.org/10.1038/nri1571
Issue Date:
DOI: https://doi.org/10.1038/nri1571
This article is cited by
-
Psychosocial factors and patient and healthcare delays in large (class T3–T4) oral, oropharyngeal, and laryngeal carcinomas
BMC Cancer (2024)
-
Social Media Posts from Friends during Late Adolescence as Predictors of Young Adult Physical Health
Journal of Youth and Adolescence (2024)
-
Understanding and Addressing the Health Implications of Anti-LGBTQ+ Legislation
Occupational Health Science (2024)
-
An epigenome-wide analysis of socioeconomic position and tumor DNA methylation in breast cancer patients
Clinical Epigenetics (2023)
-
Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents
BMC Complementary Medicine and Therapies (2023)