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Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.

Jones, KG; Brull, DJ; Brown, LC; Sian, M; Greenhalgh, RM; Humphries, SE; Powell, JT; (2001) Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms. Circulation , 103 (18) pp. 2260-2265.

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Abstract

BACKGROUND: Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. METHODS AND RESULTS: We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6. We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, P=0.01). In 466 patients with small aneurysms, the frequency of the -174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis P=0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), P=0.036, and 0.51 (95% CI 0.25 to 1.00), P=0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. CONCLUSIONS: Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.

Type: Article
Title: Interleukin-6 (IL-6) and the prognosis of abdominal aortic aneurysms.
Location: United States
Keywords: Aged, Alleles, Aortic Aneurysm, Abdominal, Blood Pressure, Brachial Artery, C-Reactive Protein, Disease Progression, Electrocardiography, Female, Fibrinogen, Follow-Up Studies, Genotype, Humans, Iliac Artery, Interleukin-6, Male, Middle Aged, Polymorphism, Genetic, Predictive Value of Tests, Prognosis, Promoter Regions, Genetic, Survival Rate, Tomography, X-Ray Computed
URI: http://discovery.ucl.ac.uk/id/eprint/97218
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