Inhibition of interleukin-1 suppresses angiotensin II-induced aortic inflammation and aneurysm formation

Abstract Background Angiotensin II (Ang II) activates components of the inflammatory cascade, which promotes hypertension and development of abdominal aortic aneurysm (AAA). This study aimed to elucidate the effects of an IL-1 receptor antagonist (IL-1Ra) and an anti-IL-1β antibody (01BSUR) on Ang II-induced AAA. Methods and results Male wild-type (WT) and IL-1Ra-deficient (IL-1Ra − / − ) mice were infused with Ang II (1000 ng/kg/min) using subcutaneous osmotic pumps for 28 days. Fourteen days post-infusion, both systolic blood pressure (SBP) (Ang II-treated IL-1Ra − / − :149 ± 2 vs. Ang II-treated WT:126 ± 3 mm Hg, p  − / − mice than in WT mice. Because 28-day infusion with Ang II in IL-1Ra −/− mice significantly increased the occurrence of fatal aortic rupture (89% vs. 6%, p  − / − mice than in WT mice (p  − / − and WT mice (117 ± 4 vs. 115 ± 3 mm Hg, p = 0.71 (after cessation of Ang II infusion)). Histological analyses showed numerous inflammatory cells around the abdominal aorta in IL-1Ra − / − mice, but not in WT mice. Finally, compared with IgG2a treatment, treatment with 01BSUR decreased Ang II-induced AAA in IL-1Ra − / − mice. Conclusions The present study demonstrates that inhibition of IL-1β significantly suppresses AAA formation after Ang II infusion, suggesting that suppression of IL-1β may provide an additional strategy to protect against AAA in hypertensive patients.