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

Objective: To 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. Methods: Serum IL-1-alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, IFN-gamma, IP-10, MCP-1, TNF-alpha, and TNF-beta 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. Results: Only IL-1 alpha (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/mm(2) into the subendothelial cell space. Post-EVAR serum was significantly less effective (44.4 +/- 10.2 neutrophils/mm(2)). This reduction in neutrophil recruitment correlated with reduced IL-1 alpha in post-EVAR serum. The addition of a neutralizing antibody against IL-1 alpha to pre-EVAR serum inhibited EC priming and neutrophil recruitment, strongly implying that this cytokine was the priming agent. Conclusion: EVAR reduces serum IL-1 alpha and its inflammatory activity in patient serum. IL-1 alpha is, therefore, implicated in the molecular pathology of AAAs and may have potential as a clinically useful biomarker. (J Vase Surg 2011;54: 497-503.)