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Chronic stress and age-related increases in the proinflammatory cytokine IL-6
Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R.. Proceedings of the National Academy of Sciences of the United States of America, 2003-07-02
Topic: Brain proteins, microglia and lab models
Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.
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APA 7th
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Malarkey, W. B., & Glaser, R. (2003). Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the National Academy of Sciences of the United States of America. https://doi.org/10.1073/pnas.1531903100
Vancouver
Kiecolt-Glaser JK, Preacher KJ, MacCallum RC, Atkinson C, Malarkey WB, Glaser R. Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proceedings of the National Academy of Sciences of the United States of America. 2003. doi:10.1073/pnas.1531903100. PMID: 12840146.
BibTeX
@article{kiecoltglaser2003-12840146,
author = {Kiecolt-Glaser, J. K. and Preacher, K. J. and MacCallum, R. C. and Atkinson, C. and Malarkey, W. B. and Glaser, R.},
title = {{Chronic stress and age-related increases in the proinflammatory cytokine IL-6}},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2003},
doi = {10.1073/pnas.1531903100},
pmid = {12840146},
url = {https://doi.org/10.1073/pnas.1531903100}
}
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Key findings
- Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline.
- Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years.
Why it matters
In this longitudinal study, caregivers of spouses with dementia had an average rate of increase in the inflammatory cytokine IL-6 about four times as large as noncaregivers, and this steeper rise persisted even years after the spouse's death. It describes a possible mechanism linking chronic stress to inflammation, not a treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 62/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Proceedings of the National Academy of Sciences of the United States of America) |
| Journal's citation record | 4 / 4 | Proceedings of the National Academy of Sciences: journal h-index 1,167 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2003 — older than 20 years, still counted |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 1,215 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 48.6 citations a year over 25 year(s) since 2003 |
| Impact for its field and year | 4 / 6 | Cited 14.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 11 other studies in this library |
| Still being cited | 3 / 4 | Cited 103 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ronald Glaser: h-index 119 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of North Carolina at Chapel Hill: institution h-index 1,674 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12840146) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 62 / 100 | — |
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