Cytokine signatures in atherosclerotic claudicants.

Abstract

BACKGROUND:

Iron accumulation and inflammation may affect atherosclerosis. This study intended to define a cytokine signature in atherosclerotic claudicants and to determine whether reduction in serum ferritin by phlebotomy influenced this pattern.

METHODS:

Ninety-one subjects with peripheral vascular disease (PVD; mean age, 67 years) were recruited from the VA Cooperative Iron and Atherosclerosis Study (FeAST) testing the hypothesis that ferritin reduction to 25 ng/ml may ameliorate atherosclerosis. Cytokines TNF-a, IL-2, IL-6, and IL-10 were analyzed by enzyme amplified sensitivity assay (EASIA). Fasting iron and cholesterol panels, complete blood count, C-reactive protein (CRP), uric acid, fibrinogen, glucose, and hemoglobin A1c levels were also quantified. Values were compared with "healthy" controls (n = 21; mean age, 56 years). After randomization of PVD to phlebotomy (intervention group [IG], n = 44) or control (nonintervention group [NG], n = 47), analyses were compared at 6 and 12 months using t test, Wilcoxon rank sum test, chi-square, and robust MM regression.

FINDINGS:

Age, glucose, and hemoglobin A1c were higher in PVD compared with healthy controls (P < 0.01), whereas serum iron (P < 0.01) and percentage of transferrin saturation (P < 0.05) were lower. Tumor necrosis factor-alpha (TNF-alpha; P < 0.05), IL-6 (P < 0.01), and CRP (P < 0.05) levels were higher in the PVD group, whereas IL-10 was lower (P < 0.01). At 6 months post phlebotomy, ferritin levels were reduced (P < 0.01), although ferritin levels were reduced less in smokers. IL-6 and fibrinogen, CRP and ferritin levels correlated positively. At 6 and 12 months, subjects with TNF-alpha (n= 15) and IL-6 (n = 10) levels in the upper 25th percentile were reduced by phlebotomy.

INTERPRETATION:

An inflammatory cytokine signature exists in atherosclerosis. Elevated levels of TNF-alpha and IL-6, reportedly associated with recurrent and future myocardial infarction, were reduced by phlebotomy. The utility of the iron/inflammatory hypotheses will ultimately relate to clinical outcomes obtained prospectively by the FeAST trial.

• Authors: Ralph G DePalma, Virginia W Hayes, H Treat Cafferata, Hamid A Mohammadpour, Bruce K Chow, Leo R Zacharski, Mark R Hall
• Journal: The Journal of surgical research (J Surg Res) Vol. 111 Issue 2 Pg. 215-21 (May 15 2003) ISSN: 0022-4804 [Print] United States
• PMID: 12850465 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)

Chemical References

• Blood Glucose
• Cytokines
• Glycated Hemoglobin A
• Interleukin-2
• Interleukin-6
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Fibrinogen
• C-Reactive Protein
• Ferritins
• Cholesterol
• Iron

Topics

• Aged
• Aged, 80 and over
• Aging
• Arteriosclerosis (blood, therapy)
• Blood Glucose (analysis)
• C-Reactive Protein (analysis)
• Cholesterol (blood)
• Cytokines (blood)
• Ferritins (blood)
• Fibrinogen (analysis)
• Glycated Hemoglobin (analysis)
• Humans
• Interleukin-10 (blood)
• Interleukin-2 (blood)
• Interleukin-6 (blood)
• Iron (blood)
• Middle Aged
• Peripheral Vascular Diseases (blood)
• Phlebotomy
• Tumor Necrosis Factor-alpha (analysis)