title: Endovascular aneurysm repair reverses the increased titer and the inflammatory activity of interleukin-1α in the serum of patients with abdominal aortic aneurysm.
abstract: 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-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.
  
  
  RESULTS
  Only 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/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-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.
  
  
  CONCLUSIONS
  EVAR 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.
authors.affiliation: School of Clinical and Experimental Medicine, The University of Birmingham, Birmingham, UK.
authors.forename: Clara M
authors.initials: CM
authors.lastname: Yates
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelhamid
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Adam
authors.forename: Gerard B
authors.initials: GB
authors.lastname: Nash
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Bradbury
authors.forename: G Ed
authors.initials: GE
authors.lastname: Rainger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000276:immunology / Q000601:surgery*; D001027:Aortography / Q000379:methods; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002448:Cell Adhesion; D002478:Cells, Cultured; D015536:Down-Regulation; D042783:Endothelial Cells / Q000276:immunology; D057510:Endovascular Procedures; D004739:England; D006801:Humans; D007118:Immunoassay; D018836:Inflammation Mediators / Q000097:blood*; D053582:Interleukin-1alpha / Q000097:blood*; D018715:Microscopy, Video; D009504:Neutrophils / Q000276:immunology; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D057705:Transendothelial and Transepithelial Migration; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha