Wang Qiong, Hermannsson Kristján, Másson Egill, Bergman Peter, Guðmundsson Guðmundur Hrafn
Faculty of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, Iceland.
Akthelia Pharmaceuticals, Grandagardi 16, 101 Reykjavik, Iceland.
Blood Rev. 2025 Mar;70:101255. doi: 10.1016/j.blre.2024.101255. Epub 2024 Dec 13.
Patients with hematologic malignancies (HM) are highly susceptible to bloodstream infection (BSI), particularly those undergoing treatments such as chemotherapy. A common and debilitating side effect of chemotherapy is oral and intestinal mucositis. These Patients are also at high risk of developing sepsis, which can arise from mucosal barrier injuries and significantly increases mortality in these patients. While conventional antibiotics are effective, their use can lead to antimicrobial resistance (AMR) and disrupt the gut microbiota (dysbiosis). In this review, we discuss utilizing host defense peptides (HDPs), key components of the innate immune system, and immune system inducers (ISIs) to maintain mucosal barrier integrity against infection, an underexplored host-directed therapy (HDT) approach to prevent BSI and sepsis. We advocate for the discovery of potent and safe ISIs for clinical use and call for further research into the mechanisms by which these ISIs induce HDPs and strengthen mucosal barriers.
血液系统恶性肿瘤（HM）患者极易发生血流感染（BSI），尤其是那些正在接受化疗等治疗的患者。化疗常见且使人虚弱的副作用是口腔和肠道黏膜炎。这些患者发生脓毒症的风险也很高，脓毒症可能源于黏膜屏障损伤，并显著增加这些患者的死亡率。虽然传统抗生素有效，但使用它们会导致抗菌药物耐药性（AMR）并破坏肠道微生物群（生态失调）。在本综述中，我们讨论利用宿主防御肽（HDPs）（先天免疫系统的关键组成部分）和免疫系统诱导剂（ISIs）来维持黏膜屏障完整性以抵御感染，这是一种尚未充分探索的宿主导向疗法（HDT），用于预防BSI和脓毒症。我们主张发现用于临床的强效且安全的ISIs，并呼吁进一步研究这些ISIs诱导HDPs并加强黏膜屏障的机制。
