Abstract 12252: The IL-23/IL-17 Axis Plays a Pro-Inflammatory Role in the Pathogenesis of Experimental Aortic Aneurysms
Introduction: The pathogenesis of aortic aneurysm (AA) formation involves chronic inflammation. The IL-23/IL-17 axis promotes inflammation in other injury models but its role in AA is unknown.
Hypothesis: We hypothesize that IL-23/IL-17 axis mediates inflammation and contributes to AA formation.
Methods: AAs were induced in 8- to 12-week old C57BL/6 (WT), IL-23-/- or IL-17-/- mice using an elastase-perfusion (or heat inactivated elastase as control) abdominal AA mouse model. The abdominal aorta was perfused for 5 minutes with 0.4 U/mL type 1 porcine pancreatic elastase. On days 3, 7 and 14 following perfusion, the abdominal aorta was measured by video micrometry and expressed as percentage increase over baseline aortic diameter (AD). Cytokine/chemokine analysis of aortic tissue was performed by multiplex-bead based ELISA. Flow cytometry analysis was used to determine cell counts. Groups were compared using ANOVA followed by Bonferroni post hoc test.
Results: There was no significant change in the percentage increase in AD between the elastase-perfused WT mice and controls on days 3 and 7. However, AD was significantly increased on day 14 in elastase-perfused WT mice compared to controls (141.1±16.2% vs 51.2±4.15%; n=5). More importantly, the elastase-perfused IL-23-/- (n=5) and IL-17-/- mice (n=9) had a significant attenuation in AD compared to elastase-perfused WT mice (n=5) (88.5± 13.8% and 89.5±7.5% vs 141.1±16.2%, respectively; p<0.05). A significant attenuation of pro-inflammatory cytokines/chemokines (IL-17, MCP-1, RANTES, MIP-1α, IFN-γ, TNF-α and KC) production occurred in the aortic tissue from elastase-perfused IL-23-/- and IL-17-/- mice compared to elastase-perfused WT mice on day 14. Moreover, a significant increase in CD4+ T cells (1.4 fold; p<0.05) and CD8+ T cells (1.3 fold; p<0.05) occurred in the aortic tissue of elastase-perfused WT mice compared to controls on day 3.
Conclusions: The IL-23/IL-17 axis plays a critical pro-inflammatory role in AA formation. The early increase in cellular infiltration of T lymphocytes may likely be a source of IL-17, which subsequently contributes to the pathogenesis of AA. In conclusion, this study provides novel evidence for a pivotal role of IL-17 in the inflammatory cascade of AA formation.
- © 2011 by American Heart Association, Inc.