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

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 < 0.001) and abdominal aortic width (0.94 ± 0.09 vs. 0.49 ± 0.03 mm, p < 0.001) were significantly higher in IL-1Ra ^{− / −} 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 < 0.0001), both types of mice were infused with Ang II for only 14 days, and histological analyses were performed at 28 days. Interestingly, AAA increased more significantly in IL-1Ra ^{− / −} mice than in WT mice (p < 0.001), although SBP did not differ at 28 days in IL-1Ra ^{− / −} 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.