Conran Nicola, Belcher John D
Hematology Center, University of Campinas - UNICAMP, Cidade Universitária, Campinas-SP, Brazil.
Department of Medicine, Division of Hematology, Oncology and Transplantation, Vascular Biology Center, University of Minnesota, Minneapolis, MN, USA.
Clin Hemorheol Microcirc. 2018;68(2-3):263-299. doi: 10.3233/CH-189012.
The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.
导致镰状细胞病（SCD）的主要β-珠蛋白基因突变具有显著的病理生理后果，可引发溶血事件并诱导炎症过程，最终导致血管阻塞。炎症过程不仅在引发SCD特有的急性疼痛性血管阻塞发作中起作用，也是该疾病许多并发症的关键组成部分，包括自体脾切除、急性胸综合征、肺动脉高压、腿部溃疡、肾病和中风。在此，我们讨论引发该疾病炎症的事件，以及传播这些炎症过程的机制、炎症分子和细胞。鉴于炎症在SCD病理生理学中所起的核心作用，目前许多处于临床前和临床开发阶段的SCD治疗方法都致力于对抗这些炎症过程的某些方面或特定分子，并且未来有可能会看到抗炎药物与羟基脲联合使用，或者在造血干细胞移植和不断发展的基因治疗对某些SCD患者不可行的情况下，替代羟基脲使用。
