Thanigaimani Shivshankar, Ibrahim Muhammad, Golledge Jonathan
The Queensland Research Centre for Peripheral Vascular Disease (QRC-PVD), College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
The Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD 4811, Australia.
Biomedicines. 2022 Sep 26;10(10):2409. doi: 10.3390/biomedicines10102409.
Inflammation is strongly implicated in the pathogenesis of abdominal aortic aneurysms (AAA). This review examined the potential role of biologic disease-modifying anti-rheumatic drugs (bDMARDs) as repurposed drugs for treating AAA. Published evidence from clinical and preclinical studies was examined. Findings from animal models suggested that a deficiency or inhibition of tumour necrosis factor-α (TNF-α) (standard mean difference (SMD): -8.37, 95% confidence interval (CI): -9.92, -6.82), interleukin (IL)-6 (SMD: -1.44, 95% CI: -2.85, -0.04) and IL-17 (SMD: -3.36, 95% CI: -4.21, -2.50) led to a significantly smaller AAA diameter compared to controls. Human AAA tissue samples had significantly increased TNF-α (SMD: 1.68, 95% CI: 0.87, 2.49), IL-1β (SMD: 1.93, 95% CI: 1.08, 2.79), IL-6 (SMD: 2.56, 95% CI: 1.79, 3.33) and IL-17 (SMD: 6.28, 95% CI: 3.57, 8.99) levels compared to non-AAA controls. In human serum, TNF-α (SMD: 1.11, 95% CI: 0.25, 1.97) and IL-6 (SMD: 1.42, 95% CI: 0.91, 1.92) levels were significantly elevated compared to non-AAA controls. These findings implicate TNF-α, IL-17 and IL-6 in AAA pathogenesis. Randomised controlled trials testing the value of bDMARDs in limiting AAA growth may be warranted.
炎症与腹主动脉瘤(AAA)的发病机制密切相关。本综述探讨了生物性改善病情抗风湿药(bDMARDs)作为 repurposed 药物治疗 AAA 的潜在作用。研究了临床和临床前研究的已发表证据。动物模型的研究结果表明,肿瘤坏死因子-α(TNF-α)(标准平均差(SMD):-8.37,95%置信区间(CI):-9.92,-6.82)、白细胞介素(IL)-6(SMD:-1.44,95%CI:-2.85,-0.04)和 IL-17(SMD:-3.36,95%CI:-4.21,-2.50)的缺乏或抑制导致与对照组相比,AAA 直径显著更小。与非 AAA 对照组相比,人类 AAA 组织样本中 TNF-α(SMD:1.68,95%CI:0.87,2.49)、IL-1β(SMD:1.93,95%CI:1.08,2.79)、IL-6(SMD:2.56,95%CI:1.79,3.33)和 IL-17(SMD:6.28,95%CI:3.57,8.99)水平显著升高。在人类血清中,与非 AAA 对照组相比,TNF-α(SMD:1.11,95%CI:0.25,1.97)和 IL-6(SMD:1.42,95%CI:0.91,1.92)水平显著升高。这些发现表明 TNF-α、IL-17 和 IL-6 与 AAA 的发病机制有关。可能有必要进行随机对照试验来测试 bDMARDs 在限制 AAA 生长方面的价值。