Humphries Chris, Addison Melisande L, Dear James W, Forbes Stuart J
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Drive, Edinburgh, UK.
Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 4-5 Little France Drive, Edinburgh, EH16 4UU, UK.
Arch Toxicol. 2025 Jan;99(1):103-114. doi: 10.1007/s00204-024-03892-2. Epub 2024 Nov 6.
Acute liver injury (ALI) has a clear requirement for novel therapies. One emerging option is the use of alternatively activated macrophages (AAMs); a distinct subtype of macrophage with a role in liver injury control and repair. In this comprehensive review, we provide an overview of the current limited options for ALI, and the potential advantages offered by AAMs. We describe the evidence supporting their use from in vitro studies, pre-clinical animal studies, and human clinical trials. We suggest why the first evidence for the clinical use of AAMs is likely to be found in acetaminophen toxicity, and discuss the specific evidence for AAM use in this population, as well as potential applications for AAMs in other patient populations. The key domains by which the performance of AAMs for the treatment of ALI will be assessed are identified, and remaining challenges to the successful delivery of AAMs to clinic are explored.
急性肝损伤（ALI）对新型治疗方法有明确需求。一种新兴的选择是使用交替活化巨噬细胞（AAMs）；这是巨噬细胞的一种独特亚型，在肝脏损伤控制和修复中发挥作用。在这篇全面综述中，我们概述了目前针对ALI的有限治疗选择，以及AAMs所具有的潜在优势。我们描述了来自体外研究、临床前动物研究和人类临床试验中支持使用AAMs的证据。我们指出为何AAMs临床应用的首个证据可能在对乙酰氨基酚毒性方面被发现，并讨论在该人群中使用AAMs的具体证据，以及AAMs在其他患者人群中的潜在应用。确定了评估AAMs治疗ALI效果的关键领域，并探讨了将AAMs成功应用于临床所面临的剩余挑战。
