Plasma cytokines, metabolic syndrome, and atherosclerosis in humans

Muredach P. Reilly, Anand Rohatgi, Kimberly McMahon, Megan L. Wolfe, Shailesh C. Pinto, Thomas Rhodes, Cynthia Girman, Daniel J. Rader

Research output: Contribution to journalArticle

34 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalJournal of Investigative Medicine
Issue number1
StatePublished - Jan 2007


  • Atherosclerosis
  • Cytokines
  • Metabolic syndrome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Reilly, M. P., Rohatgi, A., McMahon, K., Wolfe, M. L., Pinto, S. C., Rhodes, T., Girman, C., & Rader, D. J. (2007). Plasma cytokines, metabolic syndrome, and atherosclerosis in humans. Journal of Investigative Medicine, 55(1), 26-35.