Aortic aneurysms secrete interleukin-6 into the circulation

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Abstract

Objective:

Circulating plasma interleukin-6 (IL-6) concentrations are elevated in patients with abdominal aortic aneurysms (AAAs) compared with controls. In vitro studies suggest that the aneurysm is the source of the IL-6. Because IL-6 is an independent risk factor for cardiovascular mortality, elevation of this cytokine may be significant in these patients, who represent a group at increased risk from cardiovascular death. The aim of this study was to directly measure in vivo aortic IL-6 concentrations, testing the hypothesis that aneurysms secrete IL-6 into the circulation.

Methods:

Before endovascular aneurysm repair took place, blood was sampled from the entire length of the aorta in 27 patients with AAA and nine with thoracic aneurysms (TAs). A control group consisted of 15 patients without aneurysms undergoing angiography. Plasma IL-6 was determined using enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (hs-CRP) was measured turbidimetrically. Aneurysm surface area was calculated from axial computed tomography scans.

Results:

Mean IL-6 concentrations (pg/mL) were higher in the TA and AAA groups compared with controls (10.4 ± 3.7 and 4.9 ± 0.5 vs 2.7 ± 0.5,P= .002). There was a significant difference in plasma IL-6 concentration corresponding to aneurysm position in the AAA (P= .002) and TA (P= .008) groups, with both patterns conforming to a linear trend. This pattern was not observed in the control group, in which no significant difference in IL-6 concentrations was found throughout the aorta. Peak IL-6 occurred earlier in TAs compared with AAAs (descending aorta vs iliac artery) corresponding to aneurysm position (P= .0007). Linear regression revealed a positive correlation between aneurysm surface area and mean plasma IL-6 (Spearman's correlation,P= .003). The mean surface areas of the TAs, at 0.07 m2 (interquartile range [IQR], 0.06 to 0.09), were higher than those of the AAAs at 0.03 m2 (IQR, 0.02 to 0.04;P= .002). High-sensitivity CRP was within normal limits, and no significant differences were found between the AAA group and the controls.

Conclusions:

Circulating IL-6 is elevated within the aorta in patients with aneurysms and corresponds to aneurysm position. Furthermore, aneurysm surface area and mean plasma IL-6 are correlated. In the absence of any evidence of systemic inflammation in the form of elevated hs-CRP, these data support the hypothesis that aneurysms secrete IL-6 into the circulation. This may contribute to the high cardiovascular mortality observed in patients with aneurysms.

Clinical Relevance:

Abdominal aortic aneurysms (AAAs) are characterized histologically by widespread inflammation, with IL-6 playing a central role. IL-6 is secreted by AAAs in vitro, and elevated IL-6 is an independent risk factor for cardiovascular mortality. This may be clinically important in this group of patients with significant comorbidities at high risk of cardiovascular death. This study supports the hypothesis that aneurysms secrete IL-6 into the systemic circulation and suggests that the aneurysms may have more insidious effects upon cardiovascular health than solely that of rupture.

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