Abstract 306: A Protective Role of IL-1 beta in Abdominal Aortic Aneurysms

Abstract

Objectives: Abdominal aortic aneurysm (AAA) is a chronic disease characterized by persistent inflammation maintained by an array of inflammatory cells and mediators. Interleukin 1 beta (IL-1β) has largely been considered a pro-inflammatory cytokine but, interestingly, our previous studies of human AAAs showed that activated T-cells from patients with AAAs expressed lower levels of IL-1β compared to matched control patients without AAAs. This led us to hypothesize that IL-1β could have a protective role in preventing the development of AAA. Methods: Abdominal aortic aneurysms were induced in IL-1 receptor KO (IL-1R -/- ) and control mice using the CaCl 2 murine model of AAA. Mice were sacrificed six weeks after aneurysm induction. Aortic diameters were measured and compared at the time of aneurysm induction and sacrifice. Aortic samples were further evaluated histologically using connective tissue staining to assess the aortic structure in both groups. Results: At the time of sacrifice, IL-1R -/- mice demonstrated a 73.9 ± 3.3% increase in aortic diameter compared to a 25.9 ± 5.8% increase in wild type control mice (p<0.05). On histology, IL-1R -/- mice had more severe disruption of the aortic architecture compared to control mice. These data suggest that in the absence of IL-1β signaling, mice are more susceptible to aneurysms and develop more severe pathology. Conclusion: The current mouse data, in combination with our previous human studies, suggest a protective role for IL-1β in abdominal aortic aneurysm. These results are unexpected given that related pro-inflammatory cytokines TNF-α and IFN-γ both promote aneurysm formation.