Plasma cytokines, metabolic syndrome, and atherosclerosis in humans.
BACKGROUND
Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) integrate inflammatory and adipose signaling but also have direct vascular effects. We hypothesized that plasma levels of IL-6 and soluble tumor necrosis factor alpha 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.
Reilly
Muredach P
MP
Cardiovascular Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160, USA. muredach@spirit.gcrc.upenn.edu
Rohatgi
Anand
A
McMahon
Kimberly
K
Wolfe
Megan L
ML
Pinto
Shailesh C
SC
Rhodes
Thomas
T
Girman
Cynthia
C
Rader
Daniel J
DJ
D000328:Adult; D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging; D002097:C-Reactive Protein / Q000032:analysis; D002114:Calcinosis / Q000000981:diagnostic imaging; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein