Royal Columbian Hospital, 330 E Columbia St., New Westminster, BC, V3L 3W7, Canada.
Montreal Heart Institute, Montreal, QC, H1T 1C8, Canada.
Curr Atheroscler Rep. 2018 Sep 15;20(11):53. doi: 10.1007/s11883-018-0754-6.
The purpose of this review was to examine the role of IL-1β in the inflammatory process central to the development of atherosclerosis and to discuss current clinical evidence for treatments targeting IL-1β in coronary artery disease.
IL-1β has been shown to modulate atherosclerotic plaque progression by upregulating the synthesis of adhesion molecules on endothelial cells, as well increasing activation and proliferation of vascular smooth muscle cells. Animal studies have further suggested that alterations in the balance between agonists and antagonists of IL-1β are important in promoting atherosclerosis. In humans, preliminary assessment of therapy targeting IL-1β noted early reductions in serum inflammatory biomarkers among those with systemic inflammatory or coronary artery disease. The CANTOS trial, a large randomized double-blind study found that canakinumab, a monoclonal antibody targeting IL-1β, reduced ischemic events in patients being treated for secondary prevention. Cellular, animal, and now clinical studies have suggested a role for therapies aimed at IL-1β for treatment of CAD. However, given potential side effects and costs of these medications, further study is required to determine which patients may be most suited for treatment above current standard of care.
本综述旨在探讨白细胞介素-1β(IL-1β)在动脉粥样硬化发展过程中的炎症反应中的作用,并讨论针对冠状动脉疾病(CAD)中 IL-1β 的治疗的现有临床证据。
IL-1β 通过上调内皮细胞上粘附分子的合成,以及增加血管平滑肌细胞的激活和增殖,被证明可以调节动脉粥样硬化斑块的进展。动物研究进一步表明,IL-1β 的激动剂和拮抗剂之间平衡的改变对于促进动脉粥样硬化的发生非常重要。在人类中,针对 IL-1β 的治疗的初步评估注意到,那些具有全身炎症或 CAD 的患者的血清炎症生物标志物早期降低。CANTOS 试验是一项大型随机双盲研究,发现针对 IL-1β 的单克隆抗体卡那单抗可降低接受二级预防治疗的患者的缺血事件。细胞、动物,现在的临床研究表明,针对 IL-1β 的治疗方法可能对 CAD 的治疗有效。然而,鉴于这些药物的潜在副作用和成本,需要进一步研究来确定哪些患者最适合在现有治疗标准之上进行治疗。