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


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.
Jones
K G
KG
Department of Vascular Surgery, Imperial College at Charing Cross Hospital, Rayne Institute, London, UK.
Brull
D J
DJ
Brown
L C
LC
Sian
M
M
Greenhalgh
R M
RM
Humphries
S E
SE
Powell
J T
JT
D000368:Aged; D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000175:diagnosis*; D001794:Blood Pressure; D001916:Brachial Artery; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D004562:Electrocardiography; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007083:Iliac Artery; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D015996:Survival Rate; D014057:Tomography, X-Ray Computed
D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein