Kyaw Tin, Drummond Grant, Bobik Alex, Peter Karlheinz
Inflammation and Cardiovascular Disease Laboratory, Baker Heart and Diabetes Institute.
Centre for Inflammatory Diseases, Monash Medical Centre, Monash University, Melbourne, Australia.
Expert Opin Ther Targets. 2023 Mar;27(3):225-238. doi: 10.1080/14728222.2023.2193330. Epub 2023 Mar 22.
Myocarditis is a severe lymphocyte-mediated inflammatory disorder of the heart, mostly caused by viruses and immune checkpoint inhibitors (ICIs). Recently, myocarditis as a rare adverse event of mRNA vaccines for SARS-CoV-2 has caused global attention. The clinical consequences of myocarditis can be very severe, but specific treatment options are lacking or not yet clinically proven.
This paper offers a brief overview of the biology of viruses that frequently cause myocarditis, focusing on mechanisms important for viral entry and replication following host infection. Current and new potential therapeutic targets/strategies especially for viral myocarditis are reviewed systematically. In particular, the immune system in myocarditis is dissected with respect to infective viral and non-infective, ICI-induced myocarditis.
Vaccination is an excellent emerging preventative strategy for viral myocarditis, but most vaccines still require further development. Anti-viral treatments that inhibit viral replication need to be considered following viral infection in host myocardium, as lower viral load reduces inflammation severity. Understanding how the immune system continues to damage the heart even after viral clearance will define novel therapeutic targets/strategies. We propose that viral myocarditis can be best treated using a combination of antiviral agents and immunotherapies that control cytotoxic T cell activity.
心肌炎是一种由淋巴细胞介导的严重心脏炎症性疾病，主要由病毒和免疫检查点抑制剂（ICI）引起。最近，心肌炎作为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）信使核糖核酸（mRNA）疫苗的一种罕见不良事件已引起全球关注。心肌炎的临床后果可能非常严重，但缺乏特异性治疗方案或这些方案尚未得到临床验证。
本文简要概述了常引起心肌炎的病毒生物学，重点关注宿主感染后病毒进入和复制的重要机制。系统综述了尤其是针对病毒性心肌炎的现有及新的潜在治疗靶点/策略。特别是，针对感染性病毒性心肌炎和非感染性、ICI诱导的心肌炎，剖析了心肌炎中的免疫系统。
疫苗接种是病毒性心肌炎一种出色的新兴预防策略，但大多数疫苗仍需进一步研发。在宿主心肌发生病毒感染后，需要考虑采用抑制病毒复制的抗病毒治疗，因为较低的病毒载量可降低炎症严重程度。了解即使在病毒清除后免疫系统如何继续损害心脏将确定新的治疗靶点/策略。我们建议，联合使用抗病毒药物和控制细胞毒性T细胞活性的免疫疗法可最佳地治疗病毒性心肌炎。
