Endovascular aneurysm repair reverses the increased titer and the inflammatory activity of interleukin-1α in the serum of patients with abdominal aortic aneurysm

ObjectiveTo examine serum cytokine/chemokine profiles before and 6 months after endovascular repair (EVAR) of abdominal aortic aneurysm (AAA) and to determine whether they correlate with serum inflammatory activity using an in vitro model of leukocyte recruitment.MethodsSerum IL-1-α, IL-1β, IL-4, IL-6, IL-8, IL-10, IFN-γ, IP-10, MCP-1, TNF-α, and TNF-β were measured using a cytometry-based immunoassay. To test patient serum for direct inflammatory activity, human endothelial cells (EC) were stimulated with 30% patient serum for 24 hours. To test patient serum for the ability to prime EC for inflammatory responses, EC were incubated with 30% patient serum for 24 hours, followed by stimulation with low-dose (5 U/mL) TNF for 4 hours. Under both regimens of stimulation, the degree of EC activation was assessed by assaying neutrophil recruitment in a flow-based model.ResultsOnly IL-1α (67.9 ± 10.4 pg/mL vs 41.9 ± 7.4 pg/mL) and IL-8 (51.5 ± 5.1 vs 32.6 ± 4.7 pg/mL) changed significantly after surgery. Patient serum alone was unable to activate EC. However, serum from both time points could prime EC responses to low-dose TNF. Thus, after priming with preoperative serum, EC stimulated with TNF could recruit 76.7 ± 12.0 neutrophils/mm2 into the subendothelial cell space. Post-EVAR serum was significantly less effective (44.4 ± 10.2 neutrophils/mm2). This reduction in neutrophil recruitment correlated with reduced IL-1α in post-EVAR serum. The addition of a neutralizing antibody against IL-1α to pre-EVAR serum inhibited EC priming and neutrophil recruitment, strongly implying that this cytokine was the priming agent.ConclusionEVAR reduces serum IL-1α and its inflammatory activity in patient serum. IL-1α is, therefore, implicated in the molecular pathology of AAAs and may have potential as a clinically useful biomarker.

Clinical RelevanceContinuing uncertainty exists over which patients will benefit from abdominal aortic aneurysm (AAA) repair in addition to medical therapy as well as which repair method, open or endovascular, is the most clinically and cost-effective. Greater understanding of AAA development and progression, and the subsequent identification of biomarkers for rupture risk, are likely to result in better selection of patients for intervention and provide better measures of successful repair. These novel data implicate interleukin (IL)-1α in the molecular pathology of AAA. Further, they suggest that IL-1α may be a predictive biomarker for AAA size as well as outcome after endovascular aneurysm repair.