Loneliness Promotes Inflammation During Acute Stress
Open accessAbstract
Although evidence suggests that loneliness may increase risk for health problems, the mechanisms responsible are not well understood. Immune dysregulation is one potential pathway: Elevated proinflammatory cytokines such as interleukin-6 (IL-6) increase risk for health problems. In our first study (N = 134), lonelier healthy adults exposed to acute stress exhibited greater synthesis of tumor necrosis factor-alpha (TNF-α) and IL-6 by peripheral blood mononuclear cells (PBMCs) stimulated with lipopolysaccharide (LPS) than their less lonely counterparts. Similarly, in the second study (N = 144), lonelier posttreatment breast-cancer survivors exposed to acute stress exhibited greater synthesis of IL-6 and interleukin-1 beta (IL-1β) by LPS-stimulated PBMCs than their counterparts who felt more socially connected. However, loneliness was unrelated to TNF-α in Study 2, although the result was in the expected direction. Thus, two different populations demonstrated that lonelier participants had more stimulated cytokine production in response to stress than less lonely participants, which reflects a proinflammatory phenotype. These data provide a glimpse into the pathways through which loneliness may affect health.
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Participants who had more feelings of trait loneliness exhibited greater LPS-stimulated production of TNFα, IL-6, and IL-1β in response to the TSST compared to those who were less lonely.
“participants who had more feelings of trait loneliness exhibited greater LPS-stimulated production of TNFα , IL-6, and IL-1 β in response to the TSST compared to those who were less lonely”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Jaremka et al., 2013
The Discussion (page not supplied) summarizes greater stimulated TNF-α, IL-6, and IL-1β production among lonelier participants across two populations. The Results (page not supplied) qualify that summary: IL-6 and IL-1β were greater in the second sample, but its TNF-α association was not significant (p = .130). IL-1β was added only in Study 2, so the claim overstates the evidence if read as saying all three findings held in the same participants. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGottman has demonstrated that the ratio of positive to negative communication behaviors is strongly predictive of long-term relationship survival.
“and Gottman [72] has demonstrated that the ratio of positive to negative communication behaviors is strongly predictive of long-term relationship survival [73, 74].”
From Could intranasal oxytocin be used to enhance relationships? Research imperatives, clinical policy, and ethical considerations (2013) · cites this paper as [74]
Our copy’s Abstract discusses social connection and loneliness, while the Results examine inflammatory responses to acute stress. Searches for Gottman, positive-to-negative communication ratios, and relationship stability found no passage addressing whether communication behaviors predict long-term relationship survival. (LLM, conf=0.76)
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Cites
The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research
Buysse, D. J., Reynolds, C. F., Monk, T. H., Berman, S. R., & Kupfer, D. J. (1989) · Psychiatry Research · doi:10.1016/0165-1781(89)90047-4 · Cited by 35,234 · see citing works
The need to belong: Desire for interpersonal attachments as a fundamental human motivation.
Baumeister, R. F., & Leary, M. R. (1995) · Psychological Bulletin · doi:10.1037//0033-2909.117.3.497 · Cited by 23,245 · see citing works
Social Relationships and Mortality Risk: A Meta-analytic Review
Holt-Lunstad, J., Smith, T. B., & Layton, J. B. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000316 · Cited by 7,272 · cited 1× · see citing works
“This effect is on par with the negative health effects of obesity and inactivity (Holt-Lunstad et al., 2010), which provides compelling evidence for the importance of close relationships for well-being.”
BackgroundValidation of a combined comorbidity index
Charlson, M., Szatrowski, T. P., Peterson, J., & Gold, J. (1994) · Journal of Clinical Epidemiology · doi:10.1016/0895-4356(94)90129-5 · Cited by 6,587 · see citing works
UCLA loneliness scale (version 3): reliability, validity, and factor structure
Russell, D. W. (1996) · Journal of Personality Assessment · doi:10.1207/s15327752jpa6601_2 · Cited by 5,800 · see citing works
Loneliness matters: a theoretical and empirical review of consequences and mechanisms
Hawkley, L. C., & Cacioppo, J. T. (2010) · Annals of Behavioral Medicine · doi:10.1007/s12160-010-9210-8 · Cited by 4,782 · see citing works
Steptoe, A., Hamer, M., & Chida, Y. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.03.011 · Cited by 1,278 · see citing works
Tracey, K. J. (2009) · Nature Reviews Immunology · doi:10.1038/nri2566 · Cited by 1,154 · cited 1× · see citing works
“Furthermore, parasympathetic activity can reduce inflammation via the cholinergic anti-inflammatory pathway that induces acetylcholine release (Tracey, 2009).”
BackgroundA mechanism converting psychosocial stress into mononuclear cell activation
Bierhaus, A., Wolf, J., Andrassy, M., Rohleder, N., Humpert, P. M., Petrov, D., Ferstl, R., von Eynatten, M., Wendt, T., Rudofsky, G., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0438019100 · Cited by 926 · see citing works
Social regulation of gene expression in human leukocytes
Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007) · Genome Biology · doi:10.1186/gb-2007-8-9-r189 · Cited by 745 · cited 1× · see citing works
“In addition, lonelier individuals exhibited more up-regulation of proinflammatory genes and down-regulation of antiinflammatory genes compared with people who were less lonely (Cole et al., 2007).”
BackgroundLoneliness in everyday life: Cardiovascular activity, psychosocial context, and health behaviors.
Hawkley, L. C., Burleson, M. H., Berntson, G. G., & Cacioppo, J. T. (2003) · Journal of Personality and Social Psychology · doi:10.1037/0022-3514.85.1.105 · Cited by 608 · see citing works
Loneliness, social network size, and immune response to influenza vaccination in college freshmen
Pressman, S. D., Cohen, S., Miller, G. E., Barkin, A., Rabin, B. S., & Treanor, J. J. (2005) · Health Psychology · doi:10.1037/0278-6133.24.3.297 · Cited by 608 · see citing works
Loneliness and stress-related inflammatory and neuroendocrine responses in older men and women
Hackett, R. A., Hamer, M., Endrighi, R., Brydon, L., & Steptoe, A. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.016 · Cited by 272 · see citing works
Flagged first, then by citations
Research works printed but not linked: 26
- Cacioppo JT Ernst JM Burleson MH McClintock MK Malarkey WB Hawkley LC Kowalewski RB 2000 Lonely traits and concomitant physiological processes: the MacArthur social neuroscience studies International Journal of Psychophysiology 35 2–3 143 154 10677643
- Cacioppo JT Hawkley LC Berntson GG Ernst JM Gibbs AC Stickgold R Hobson JA 2002 Do lonely days invade the nights? Potential social modulation of sleep efficiency Psychological Science 13 4 384 387 12137144
- Calder PC 2004 n-3 fatty acids, inflammation, and immunity--relevance to postsurgical and critically ill patients Lipids 39 12 1147 1161 15736910 PMC7101959
- Deshmane SL Kremlev S Amini S Sawaya BE 2009 Monocyte chemoattractant protein-1 (MCP-1): An overview Journal of Interferon & Cytokine Research 29 6 313 326 10.1089/jir.2008.0027 19441883 PMC2755091 · DOI · Paper page
- Dixon D Cruess S Kilbourn K Klimas N Fletcher MA Ironson G Baum A 2006 Social support mediates loneliness and human herpesvirus type 6 (HHV-6) antibody titers Journal of applied social psychology 31 6 1111 1132 10.1111/j.1559-1816.2001.tb02665.x 20407593 PMC2855978 · DOI
- Ershler WB Keller ET 2000 Age-associated increased Interleukin-6 gene expression, late-life diseases, and frailty Annual Review of Medicine 51 1 245 270 10.1146/annurev.med.51.1.245 10774463 · DOI · Paper page
- Faraut B Boudjeltia KZ Vanhamme L Kerkhofs M 2012 Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery Sleep Medicine Reviews 16 2 137 149 10.1016/j.smrv.2011.05.001 21835655 · DOI · Paper page
- Fritsche K 2006 Fatty acids as modulators of the immune response Annual Review of Nutrition 26 45 73 10.1146/annurev.nutr.25.050304.092610 16848700 · DOI
- Glaser R Kiecolt-Glaser JK 2005 Stress-induced immune dysfunction: Implications for health Nature Reviews Immunology 5 3 243 251 10.1038/nri1571 15738954 · DOI · Paper page
- Glaser R Kiecolt-Glaser JK Speicher CE Holliday JE 1985 Stress, loneliness, and changes in herpesvirus latency Journal of Behavioral Medicine 8 3 249 260 10.1007/BF00870312 3003360 · DOI
- Hansson GK 2005 Inflammation, atherosclerosis, and coronary artery disease New England Journal of Medicine 352 16 1685 1695 15843671
- Hawkley LC Bosch JA Engeland CG Marucha PT Cacioppo JT 2007 Loneliness, dysphoria, stress, and immunity: A role for cytokines Plotnikoff NP Cytokines: Stress And Immunity 67 85 CRC Press
- Kiecolt-Glaser JK Garner W Speicher C Penn GM Holliday J Glaser R 1984 Psychosocial modifiers of immunocompetence in medical students Psychosomatic Medicine 46 1 7 14 6701256
- Kiecolt-Glaser JK Ricker D George J Messick G Speicher C Garner W Glaser R 1984 Urinary cortisol levels, cellular immunocompetency, and loneliness in psychiatric inpatients Psychosomatic Medicine 46 1 15 23 6701251
- Kirschbaum C Pirke KM Hellhammer DH 1993 The “Trier Social Stress Test”--a tool for investigating psychobiological stress responses in a laboratory setting Neuropsychobiology 28 1–2 76 81 8255414
- Kohm AP Sanders VM 2000 Norepinephrine: a messenger from the brain to the immune system Immunology Today 21 11 539 542 10.1016/S0167-5699(00)017473 11094255 · DOI
- Leary MR Cox CB 2008 Belongingness motivation: A mainspring of social action Gardner WL Shah JY Handbook of Motivation Science 27 40 New York, NY Guilford Press
- Maslow AH 1968 Toward a Psychology of Being 2 Oxford, England D Van Nostrand
- Mohamed-Ali V Goodrick S Rawesh A Katz DR Miles JM Yudkin JS Klein S 1997 Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo The Journal of Clinical Endocrinology and Metabolism 82 12 4196 4200 9398739
- Shephard RJ 2002 Cytokine responses to physical activity, with particular reference to IL-6: sources, actions, and clinical implications Critical Reviews in Immunology 22 3 165 182 12498381
- Stewart AL Mills KM King AC Haskell WL Gillis D Ritter PL 2001 CHAMPS physical activity questionnaire for older adults: outcomes for interventions Medicine and Science in Sports and Exercise 33 7 1126 1141 11445760
- Strine TW Chapman DP 2005 Associations of frequent sleep insufficiency with health-related quality of life and health behaviors Sleep Medicine 6 1 23 27 10.1016/j.sleep.2004.06.003 15680291 · DOI
- Sugisawa H Liang J Liu X 1994 Social networks, social support, and mortality among older people in Japan Journal of Gerontology 49 1 S3 S13 10.1093/geronj/49.1.S3 8282987 · DOI · Paper page
- Thurston RC Kubzansky LD 2009 Women, loneliness, and incident coronary heart disease Psychosomatic medicine 71 8 836 842 10.1097/PSY.0b013e3181b40efc 19661189 PMC2851545 · DOI
- Tooby J Cosmides L 1996 Friendship and the banker's paradox: Other pathways to the evolution of adaptations for altruism Runciman WG Smith JM Dunbar RIM Evolution of Social Behaviour Patterns in Primates and Man 119 143 New York, NY Oxford University Press
- Uchino BN 2009 Understanding the links between social support and physical health: A life-span perspective with emphasis on the separability of perceived and received support Perspectives on Psychological Science 4 3 236 255 26158961
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Inflammation: Depression Fans the Flames and Feasts on the Heat
Kiecolt-Glaser, J. K., Derry, H. M., & Fagundes, C. P. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020152 · Cited by 844 · see citing works
Self-citationMarsland, A. L., Walsh, C., Lockwood, K., & John-Henderson, N. A. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.01.011 · Cited by 691 · see citing works
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Cacioppo, S., Capitanio, J. P., & Cacioppo, J. T. (2014) · Psychological Bulletin · doi:10.1037/a0037618 · Cited by 623 · see citing works
Perceived social isolation, evolutionary fitness and health outcomes: a lifespan approach
Hawkley, L. C., & Capitanio, J. P. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2014.0114 · Cited by 468 · see citing works
Pain, depression, and fatigue: Loneliness as a longitudinal risk factor.
Jaremka, L. M., Andridge, R. R., Fagundes, C. P., Alfano, C. M., Povoski, S. P., Lipari, A. M., Agnese, D. M., Arnold, M. W., Farrar, W. B., Yee, L. D., et al. (2014) · Health Psychology · doi:10.1037/a0034012 · Cited by 346 · see citing works
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Sutin, A. R., Stephan, Y., Luchetti, M., & Terracciano, A. (2020) · The Journals of Gerontology: Series B · doi:10.1093/geronb/gby112 · Cited by 331 · see citing works
Kéri, S., Szabó, C., & Kelemen, O. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.03.020 · Cited by 165 · see citing works
Nersesian, P. V., Han, H.-R., Yenokyan, G., Blumenthal, R. S., Nolan, M. T., Hladek, M. D., & Szanton, S. L. (2018) · Social Science & Medicine · doi:10.1016/j.socscimed.2018.04.007 · Cited by 120 · see citing works
Aiello, A. E., Chiu, Y.-L., & Frasca, D. (2017) · GeroScience · doi:10.1007/s11357-017-9983-9 · Cited by 73 · see citing works
Wudarczyk, O. A., Earp, B. D., Guastella, A., & Savulescu, J. (2013) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e3283642e10 · Cited by 52 · see citing works
Adams, R. N., Mosher, C. E., Rand, K. L., Hirsh, A. T., Monahan, P. O., Abonour, R., & Kroenke, K. (2017) · Quality of Life Research · doi:10.1007/s11136-017-1518-4 · Cited by 49 · see citing works
Granata, L., Gildawie, K. R., Ismail, N., Brenhouse, H. C., & Kopec, A. M. (2022) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2022.101143 · Cited by 15 · see citing works
Combined effects of social isolation and loneliness on disability incidence in older adults
Shimada, H., Doi, T., Tsutsumimoto, K., Makino, K., Harada, K., Tomida, K., Morikawa, M., & Arai, H. (2025) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2025.105749 · Cited by 9 · see citing works
- Authors
- Jaremka, L. M., Fagundes, C. P., Peng, J., Bennett, J. M., Glaser, R., Malarkey, W. B., & Kiecolt-Glaser, J. K.
- Affiliations
- The Ohio State University (US)
- The Ohio State University Wexner Medical Center (US)
- Institute for Behavioral Medicine Research, The Ohio State University College of Medicine
- Venue
- Psychological Science
- Publisher
- SAGE Publications
- Published
- 2013-04-29
- Volume
- 24
- Issue
- 7
- Pages
- 1089-1097
- ISSN
- 0956-7976 (ISSN-L)
- 1467-9280
- PMC
- PMC3825089
- OpenAlex
- W2106971338
- Cited by
- 255
- References
- 13
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 16 · 2023: 18 · 2022: 27 · 2021: 25 · 2020: 10 · 2019: 15 · 2018: 38 · 2017: 18 · 2016: 19 · 2015: 16 · 2014: 9 · 2013: 4 · 2012: 1
- FWCI
- 18.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychological Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG029562, AG029562)
- National Cancer Institute (CA016058, CA126857, R01CA126857, CA131029, R01CA131029, P30CA016058)
- National Institute of Dental and Craniofacial Research (DE-014320, T32DE014320)
- National Center for Research Resources (UL1RR025755)
- Topics
- Social Sciences › Health › Health disparities and outcomes
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- loneliness, acute stress, inflammation, inflammatory cytokines, interleukin-6, TNF-α, IL-1β, peripheral blood mononuclear cells, lipopolysaccharide stimulation, breast cancer survivors, social connectedness, immune dysregulation
- MeSH terms
- Adult, Aged, Breast Neoplasms, Female, Humans, Inflammation, Leukocytes, Mononuclear, Lipopolysaccharides, Loneliness, Male, Middle Aged, Stress, Psychological, Tumor Necrosis Factor-alpha, Interleukin-6, Survivors, Interleukin-1beta
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