Cited 15 times since 2016 (1.7 per year) source: EuropePMC Atherosclerosis, Volume 251, 11 2 2016, Pages 139-146 IL-6: A Janus-like factor in abdominal aortic aneurysm disease. Kokje VBC, Gäbel G, Koole D, Northoff BH, Holdt LM, Hamming JF, Lindeman JHN
Background and aims
An abdominal aortic aneurysm (AAA) is part of the atherosclerotic spectrum of diseases. The disease is hallmarked by a comprehensive localized inflammatory response with striking IL-6 hyperexpression. IL-6 is a multifaceted cytokine that, depending on the context, acts as a pro- or anti-inflammatory factor. In this study, we explore a putative role for IL-6 in AAA disease.
Methods
ELISA's, Western blot analysis, real time PCR and array analysis were used to investigate IL-6 expression and signaling in aneurysm wall samples from patients undergoing elective AAA repair. A role for IL-6 in AAA disease was tested through IL-6 neutralization experiments (neutralizing antibody) in the elastase model of AAA disease.
Results
We confirmed an extreme disparity in aortic wall IL-6 content between AAA and atherosclerotic disease (median [5th-95th percentile] aortic wall IL-6 content: 281.6 [0.0-1820.8] (AAA) vs. 1.9 [0.0-37.8] μg/g protein (atherosclerotic aorta), (p < 0.001). Array analysis followed by pathway analysis showed that IL-6 hyper-expression is followed by increased IL-6 signaling (p < 0.000039), an observation confirmed by higher aneurysm wall pSTAT3 levels, and SOCS1 and SOCS3 mRNA expression, (p < 0.018). Remarkably, preventive IL-6 neutralization i.e. treatment started one day prior to the elastase-induction resulted in >40% 7-day mortality due to aortic rupture. In contrast, delayed IL-6 neutralization (i.e. neutralization started at day 4 after elastase induction) did not result in ruptures, and quenched AAA growth (p < 0.021).
Conclusions
AAA disease is characterized by increased IL-6 signaling. In the context of the elastase model of AAA disease, IL-6 appears a multi-faceted factor, protective upon acute injury, but negatively involved in the perpetuation of the disease process.
