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 amon g aneurysm patients, the circulating concentration of IL-6 appears to be in creased. 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 cir culating IL-6 signaled rapid aneurysm growth and (2) the -174 G-->C polymor phism in the IL-6 promoter predicted survival. For 19 patients with large o r inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this di fference increasing with aneurysm diameter, P=0.01). In 466 patients with s mall aneurysms, the frequency of the -174 C allele (0.40) was similar to th at in a normal healthy population. Patients of GC 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 p atients 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 a ssociation between plasma IL-6 or IL-6 genotype and aneurysm growth. Conclusions-Aortic aneurysms appear to be an important source of circulatin g IL-6, the concentration being influenced by genotype. For patients with s mall aneurysms, the -174 G-->C IL-6 genotype predicts future cardiovascular mortality.