Chronic interpersonal stress predicts activation of pro- and anti-inflammatory signaling pathways 6 months later
Open accessAbstract
OBJECTIVE: To understand the mechanisms underlying chronic interpersonal difficulties and their detrimental influence on mental and physical health. METHODS: A total of 103 healthy young women (mean age = 17 years) were administered a structured interview to assess the degree of chronic interpersonal stress in their lives. At the same time, blood was drawn to measure systemic inflammation, the expression of signaling molecules that regulate immune activation, and leukocyte production of the cytokine interleukin-6 after ex vivo stimulation with lipopolysaccharide. All of the immunologic assessments were repeated 6 months later. RESULTS: To the extent subjects were high in chronic interpersonal stress at baseline, their leukocytes displayed greater increases in messenger ribonucleic acid (mRNA) for the proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) over the next 6 months. They also showed larger increases in mRNA for inhibitor of kappaB, a molecule that sequesters NF-kappaB in the cytoplasm and minimizes its proinflammatory activities. Chronic interpersonal stress at baseline was unrelated to changes in biomarkers of systemic inflammation but was associated with increasingly pronounced interleukin-6 responses to lipopolysaccharide. These associations were independent of demographics, lifestyle variables, and depressive symptoms. CONCLUSIONS: These findings suggest that chronic interpersonal difficulties accentuate expression of pro- and anti-inflammatory signaling molecules. Although this process does not result in systemic inflammation under quiescent conditions, it does accentuate leukocytes' inflammatory response to microbial challenge. These dynamics may underlie the excess morbidity associated with social stress, particularly in inflammation-sensitive diseases like depression and atherosclerosis.
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In a six-month longitudinal study of adolescent females, greater interpersonal stress was associated with larger LPS-stimulated IL-6 production and bigger NF-kB increases over time.
“In a six-month longitudinal study of adolescent females, greater interpersonal stress was associated with larger lipopolysaccharide (LPS)-stimulated IL-6 production and bigger NFκB increases over time”
From Close relationships, inflammation, and health (2010) · cites this paper as Miller et al., 2009
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- Authors
- Miller, G. E., Rohleder, N., & Cole, S. W.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Miller, Gregory E.
- Venue
- Psychosomatic Medicine
- Published
- 2009-01
- Volume
- 71
- Issue
- 1
- Pages
- 57-62
- ISSN
- 0033-3174 (ISSN-L)
- PMC
- PMC2720615
- OpenAlex
- W2119581482
- Cited by
- 197
- References
- 41
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 6 · 2023: 12 · 2022: 7 · 2021: 12 · 2020: 11 · 2019: 10 · 2018: 13 · 2017: 12 · 2016: 13 · 2015: 14 · 2014: 19 · 2013: 11 · 2012: 21
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychosomatic Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA116778)
- 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
- social stress, systemic inflammation, NF-κB, IκB, interleukin-6, lipopolysaccharide response, leukocyte gene expression, young women, depression, atherosclerosis
- MeSH terms
- Adolescent, C-Reactive Protein, Chronic Disease, Conflict, Psychological, Female, Follow-Up Studies, Humans, Inflammation, Interpersonal Relations, Leukocytes, Life Style, Lipopolysaccharides, Prospective Studies, Receptors, Glucocorticoid, RNA, Messenger, Sexual Partners, Stress, Psychological, Signal Transduction, Biomarkers, Interleukin-6, NF-kappa B, I-kappa B Proteins, Friends, Family Conflict, Young Adult
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