Pediatric Hematology and Oncology Children's Hospital III, Johann Wolfgang Goethe University, Frankfurt, Germany.
Curr Pharm Des. 2013;19(20):3689-712. doi: 10.2174/1381612811319200010.
Despite the availability of new antifungal compounds, morbidity and mortality of invasive aspergillosis are still unacceptably high, in particular in immunocompromised patients such as patients with hematological malignancies or allogeneic hematopoietic stem cell or solid organ transplant recipients. Over the last decades, our knowledge of the immunopathogenesis of invasive aspergillosis has greatly advanced. This, in turn, provided critical information to augment host immunity against fungal pathogens. Potential approaches for enhancing the host immune system in the combat against Aspergillus include the administration of effector and regulatory cells (e.g., granulocytes, antigen-specific T cells, natural killer cells, dendritic cells) as well as the administration of recombinant cytokines, interferons and growth factors (e.g., interferon-γ,granulocyte- and granulocyte-macrophage colony stimulating factor) and various vaccination strategies. Although promising results are reported on in vitro data and animal studies, current data are too limited to allow solid conclusions on the risk and the benefit of these strategies in the clinical setting. Therefore, the real challenge in the future is to perform appropriately designed and powered clinical trials. These require international, multi-center collaboration, but may ultimately improve the outcome in immunocompromised patients suffering from invasive aspergillosis.
尽管有新的抗真菌化合物可用,但侵袭性曲霉菌病的发病率和死亡率仍然高得令人无法接受,特别是在免疫功能低下的患者中,如血液恶性肿瘤或异基因造血干细胞或实体器官移植受者。在过去的几十年中,我们对侵袭性曲霉菌病的免疫发病机制的认识有了很大的提高。这反过来又为增强宿主对真菌病原体的免疫力提供了关键信息。增强宿主免疫系统对抗曲霉菌的潜在方法包括施用效应细胞和调节细胞(例如粒细胞、抗原特异性 T 细胞、自然杀伤细胞、树突状细胞)以及施用重组细胞因子、干扰素和生长因子(例如干扰素-γ、粒细胞和粒细胞-巨噬细胞集落刺激因子)以及各种疫苗接种策略。尽管在体外数据和动物研究中报告了有希望的结果,但目前的数据还太有限,无法在临床环境中对这些策略的风险和益处得出确凿的结论。因此,未来的真正挑战是进行设计合理且有足够效力的临床试验。这些需要国际、多中心的合作,但最终可能会改善免疫功能低下的侵袭性曲霉菌病患者的预后。