Treatment With an Anti-IL-1β Antibody Does Not Impact Aortic Aneurysm Progression in a Rupture-Prone Rat Model

Abdominal aortic aneurysm (AAA) is a life-threatening inflammatory vascular disease with no effective medical therapies to mitigate its progression and rupture. While interleukin-1 beta (IL-1β) plays a central role in AAA pathobiology, the specific impact of its inhibition on progression and rupture remains unclear. This study evaluated whether selective antibody-mediated IL-1β inhibition can reduce aneurysm progression in a rupture-prone AAA model in rats. Infrarenal AAAs were induced in male and female Sprague-Dawley rats (N=30). The 14-day cohort included n=5 per sex/treatment group, while the day 6 inflammatory analyses included male rats only (n = 5 per treatment group). AAAs were induced using intraluminal porcine pancreatic elastase (PPE) alongside oral β-aminopropionitrile (BAPN) administration to promote AAA rupture. After 3 days, rats received a neutralizing anti-IL-1β antibody or a control IgG twice weekly. Aneurysm growth, rupture incidence, and histopathology were assessed over 14 days. Results demonstrated that treatment with anti-IL-1β antibody did not significantly impact aneurysm progression, rupture rates, collagen content, or elastin degradation in either sex. While upstream inflammatory mediators remained unchanged, in male rats assessed at day 6, treatment with the neutralizing anti-IL-1β antibody was associated with significantly reduced IL-10 and IFN-γ levels within aneurysmal tissue, alongside a trend toward reduced CD206 expression. These findings suggest that IL-1β plays a multifaceted role in maintaining counter-regulatory immune responses in established AAA, indicating that treatment with anti-IL-1β antibody did not demonstrate measurable structural benefit under the experimental conditions examined. Clinical Relevance AAA is a life-threatening condition with no effective medical treatments to prevent its progression and rupture. IL-1β is essential for AAA formation, as evidenced by the significant attenuation of aneurysm formation in IL-1β receptor knockout models. However, our study demonstrated that treatment with a neutralizing anti-IL-1β antibody did not significantly alter AAA growth or rupture rates in a rupture-prone rat model. These results indicate that anti-IL-1β antibody treatment initiated after aneurysm induction may have limited efficacy in this short-term rupture-prone model, but these findings do not exclude a potential effect of IL-1β inhibition during earlier stages of aneurysm formation. However, because pharmacodynamic target engagement was not directly quantified, incomplete IL-1β neutralization cannot be excluded.