Plasma Cytokines, Metabolic Syndrome, and Atherosclerosis in Humans
Abstract
Background: Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) integrate inflammatory and adipose signaling but also have direct vascular effects. We hypothesized that plasma levels of IL-6 and soluble tumor necrosis factor α receptor 2 (sol-TNFR2) would be related to coronary atherosclerosis beyond established risk factors and the metabolic syndrome. Methods: We examined the association of IL-6 and sol-TNFR2 with metabolic syndrome, C-reactive protein (CRP), and coronary artery calcification (CAC) in 875 asymptomatic participants in the Study of Inherited Risk of Coronary Atherosclerosis. Results: IL-6 levels were 56% higher ( p < .001) and sol-TNFR2 levels 16% higher ( p < .001) in subjects with metabolic syndrome compared with those without. Both cytokines were associated with CAC beyond age, gender, Framingham risk scores, family history, metabolic syndrome, and CRP (odds ratio and 95% confidence interval of higher CAC for 1 SD increase in log-transformed cytokine levels: 1.23 [1.06-1.43], p = .006 for IL-6 and 1.15 [1.01-1.31], p = .04 for sol-TNFR2). In fact, cytokine levels were independently associated with CAC scores in the subgroup with metabolic syndrome and were additive to the homeostasis model assessment of insulin resistance in predicting CAC. Conclusions: Plasma IL-6 and sol-TNFR2 levels were independently associated with CAC, suggesting a role in integrating innate immune and adipose signaling in promoting atherosclerosis and cardiovascular risk. Measurement of their levels may facilitate cardiovascular risk prediction and targeting of therapeutic strategies.
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Plasma concentrations of IL-6 and TNF-α predict the risk of myocardial infarction.
“Plasma concentrations of IL-6 [31] and TNF-α have been shown to predict the risk of myocardial infarction in several studies [32]”
From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [32]
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- Authors
- Reilly, M. P., Rohatgi, A., McMahon, K., Wolfe, M. L., Pinto, S. C., Rhodes, T., Girman, C., & Rader, D. J.
- Affiliations
- University of Pennsylvania (US)
- The University of Texas Southwestern Medical Center (US)
- Department of Epidemiology, Merck Research Laboratories, West Point, PA.
- ORCID
- Venue
- Journal of Investigative Medicine
- Publisher
- SAGE Publications
- Published
- 2007-01
- Volume
- 55
- Issue
- 1
- Pages
- 26-35
- ISSN
- 1081-5589 (ISSN-L)
- 1708-8267
- OpenAlex
- W1971294777
- Cited by
- 42
- References
- 69
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 2 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 1 · 2013: 3 · 2012: 1
- FWCI
- 4.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Investigative Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (M01-RR-00040, M01RR000040)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- interleukin-6, metabolic syndrome, coronary artery calcification, atherosclerosis, C-reactive protein, insulin resistance, cardiovascular risk prediction, plasma cytokines, adipose tissue inflammation, innate immunity
- MeSH terms
- Adult, C-Reactive Protein, Calcinosis, Female, Humans, Male, Middle Aged, Risk Factors, Tomography, X-Ray Computed, Tumor Necrosis Factor-alpha, Interleukin-6, Coronary Angiography, Metabolic Syndrome, Atherosclerosis
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