Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Pharmacol Ther. 2016 May;161:40-51. doi: 10.1016/j.pharmthera.2016.03.006. Epub 2016 Mar 20.
Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alteration of the immune response and antiviral treatments; however, success has been limited. Since the myocarditis treatment trials in the 1990s there has been an improved understanding of disease progression and new facets of the immune response have been discovered. This new information provides fresh opportunities to develop therapeutics to treat myocarditis. This review analyzes previous pharmacologic approaches including immunosuppression, high dose intravenous immunoglobulin treatment, immunoadsorption and antiviral treatments, and looks forward toward recently identified immune factors that can be exploited as targets for new treatments. Such strategies include bolstering beneficial regulatory T cells or mitigating the detrimental Th17 T cells which can drive autoimmunity in the heart. The surging interest of the application of humanized monoclonal antibodies makes targeting deleterious arms of the immune response like Th17 cells a tangible goal in the near future. Promising constituents of herbal remedies have also been identified that may hold potential as new pharmacological treatments for myocarditis, however, significant work remains to elucidate the pharmacokinetics and side-effects of these compounds. Finally, advances in our understanding of the function of Matrix Metalloproteinases yield another target for altering disease progression given their role in the development of fibrosis during Dilated Cardiomyopathy. In bringing to light the various new targets and treatments available since the last myocarditis treatment trials, the aim of this review is to explore the new treatments that are possible in new myocarditis treatment trials.
心肌炎是一组以心肌炎症为特征的异质性疾病。心肌炎的主要临床表现为儿童和青年的心力衰竭和猝死。已经研究了许多干预措施来治疗心肌炎，包括广谱改变免疫反应和抗病毒治疗；然而，收效甚微。自 20 世纪 90 年代以来的心肌炎治疗试验以来，人们对疾病进展有了更好的了解，并发现了免疫反应的新方面。这些新信息为开发治疗心肌炎的疗法提供了新的机会。本综述分析了以前的药理学方法，包括免疫抑制、大剂量静脉注射免疫球蛋白治疗、免疫吸附和抗病毒治疗，并展望了最近发现的可以作为新治疗靶点的免疫因子。这些策略包括增强有益的调节性 T 细胞或减轻可驱动心脏自身免疫的有害 Th17 T 细胞。应用人源化单克隆抗体的兴趣激增使得靶向免疫反应的有害臂，如 Th17 细胞，成为近期的一个切实目标。还确定了草药疗法有希望的成分，它们可能作为心肌炎的新药物治疗方法具有潜力，但仍需大量工作来阐明这些化合物的药代动力学和副作用。最后，基质金属蛋白酶功能的研究进展为改变疾病进展提供了另一个目标，因为它们在扩张型心肌病纤维化的发展中起作用。本综述旨在探讨新的心肌炎治疗试验中可能存在的新的治疗方法，旨在阐明自上次心肌炎治疗试验以来出现的各种新的治疗靶点和治疗方法。
