From the Université de Paris, Inserm U970, Paris Cardiovascular Research Center, Paris, France (H.A.-O., A.T.).
Service de Réanimation Médicale, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France (H.A.-O.).
Arterioscler Thromb Vasc Biol. 2019 Aug;39(8):1510-1519. doi: 10.1161/ATVBAHA.119.311998. Epub 2019 Jul 11.
Accumulating observations in humans and animals indicate that inflammation plays a key role in atherosclerosis development and subsequent complications. Moreover, the use of loss- or gain-of-function genetically modified, atherosclerosis-prone mice has provided strong experimental evidence for a causal role of innate and adaptive immunity in atherosclerosis and has revealed the pathogenic activity of proinflammatory cytokines, including TNF (tumor necrosis factor)-α, IL (interleukin)-1β, IL-6, and IL-18, and the atheroprotective effect of anti-inflammatory cytokines, including IL-10 and TGF-β. For the past 15 years, treatments using monoclonal antibodies specifically targeting cytokines, commonly referred as biological therapies, have transformed the treatment of chronic inflammatory diseases, such as rheumatoid arthritis or psoriasis, both conditions associated with increased cardiovascular risk. Analyzing the impact of anticytokine therapies on the cardiovascular outcomes of patients with chronic inflammatory diseases provides insight into the clinical relevance of experimental data on the role of inflammation in atherothrombotic cardiovascular diseases. CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) provided the first evidence that targeting inflammation in humans with atherosclerosis could improve clinical outcomes. Treatment with the anti-IL-1β antibody canakinumab significantly reduced recurrent cardiovascular events in individuals with stable coronary artery disease well-treated with standard-of-care measures. Other clinical studies support the protective effects of treatment with anti-TNF-α and anti-IL-6 receptor monoclonal antibodies on cardiovascular risk. Blockade of the IL-23/IL-17 axis, however, warrants caution as a cardiovascular intervention. Targeting this pathway has improved psoriasis but may augment cardiovascular risk in certain patients. Thus, careful consideration of the cardiovascular risk profile may influence the choice of the most appropriate treatment for patients with chronic inflammatory diseases.Visual Overview: An online visual overview is available for this article.
在人类和动物中的积累观察表明，炎症在动脉粥样硬化发展和随后的并发症中起着关键作用。此外，使用缺失或获得功能的基因修饰、易患动脉粥样硬化的小鼠提供了先天和适应性免疫在动脉粥样硬化中的因果作用的有力实验证据，并揭示了促炎细胞因子（包括 TNF-α、IL-1β、IL-6 和 IL-18）的致病活性，以及抗炎细胞因子（包括 IL-10 和 TGF-β）的抗动脉粥样硬化作用。在过去的 15 年中，使用专门针对细胞因子的单克隆抗体（通常称为生物疗法）进行的治疗改变了慢性炎症性疾病（如类风湿关节炎或银屑病）的治疗方法，这两种疾病都与心血管风险增加有关。分析抗细胞因子疗法对慢性炎症性疾病患者心血管结局的影响，为实验数据中炎症在动脉粥样血栓性心血管疾病中的作用的临床相关性提供了深入了解。CANTOS（Canakinumab Antiinflammatory Thrombosis Outcome Study）提供了第一个证据，表明针对动脉粥样硬化患者的炎症可以改善临床结局。用抗 IL-1β 抗体卡那单抗治疗可显著降低接受标准治疗的稳定型冠状动脉疾病患者的复发性心血管事件。其他临床研究支持抗 TNF-α 和抗 IL-6 受体单克隆抗体治疗对心血管风险的保护作用。然而，IL-23/IL-17 轴的阻断作为心血管干预措施需要谨慎。靶向该途径改善了银屑病，但可能会增加某些患者的心血管风险。因此，仔细考虑心血管风险概况可能会影响为慢性炎症性疾病患者选择最合适的治疗方法。
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