Cardiovascular Institute, Institute for Translational Medicine and Therapeutics, and Department of Medicine, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Curr Opin Lipidol. 2012 Dec;23(6):548-53. doi: 10.1097/MOL.0b013e328359b0a6.
Atherosclerosis is greatly influenced by inflammatory mediators at all phases. Recent studies have suggested a causal role of one such mediator, interleukin 1β (IL-1β), in the development of atherosclerotic vascular disease. This review highlights recent investigation of the role of IL-1β in atherosclerosis and the potential of its inhibition as a promising therapeutic strategy for the treatment of atherosclerotic vascular disease.
Studies in animals have generally shown decreased atherosclerotic plaque burden in atherosclerosis-prone mice deficient in IL-1β and increased plaque in mice exposed to excess IL-1β. In humans, IL-1β was found in greater concentrations in atherosclerotic human coronary arteries compared with normal coronary arteries. Preclinical and clinical studies of IL-1β inhibition have shown efficacy in the treatment of several inflammatory disorders, suggesting that IL-1β may be a novel therapeutic target for anti-inflammatory therapy in atherosclerosis, such as coronary artery disease (CAD).
IL-1β inhibition offers an interesting and biology-based opportunity to test the potential beneficial effects of an anti-inflammatory therapeutic strategy in patients with CAD. A large clinical trial evaluating the impact of IL-1β inhibition in CAD is ongoing and will be an important test of the inflammation hypothesis in CAD.
动脉粥样硬化在各个阶段都受到炎症介质的极大影响。最近的研究表明,一种炎症介质白细胞介素 1β(IL-1β)在动脉粥样硬化性血管疾病的发展中起因果作用。本综述强调了最近对 IL-1β 在动脉粥样硬化中的作用的研究以及抑制其作为治疗动脉粥样硬化性血管疾病的有前途的治疗策略的潜力。
动物研究通常表明,IL-1β缺乏的动脉粥样硬化易感小鼠的动脉粥样硬化斑块负担减少,而暴露于过量 IL-1β的小鼠的斑块增加。与正常冠状动脉相比,在动脉粥样硬化的人类冠状动脉中发现了更高浓度的 IL-1β。IL-1β 抑制的临床前和临床研究表明,其在治疗几种炎症性疾病方面具有疗效,这表明 IL-1β 可能是动脉粥样硬化(如冠心病 CAD)抗炎治疗的一个新的治疗靶点。
IL-1β 抑制为测试 CAD 患者抗炎治疗策略的潜在有益效果提供了一个有趣且基于生物学的机会。一项正在评估 IL-1β 抑制对 CAD 影响的大型临床试验是一个重要的测试 CAD 炎症假说的试验。