Immunomodulation Therapy for Invasive Aspergillosis: Discussion on Myeloid Growth Factors, Recombinant Cytokines, and Antifungal Drug Immune Modulation.
Immunomodulation Therapy for Invasive Aspergillosis: Discussion on Myeloid Growth Factors, Recombinant Cytokines, and Antifungal Drug Immune Modulation.
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侵袭性曲霉菌病的免疫调节治疗：关于骨髓生长因子、重组细胞因子和抗真菌药物免疫调节的讨论。
DOI：
10.1007/s12281-010-0006-x
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发表时间：
2010
影响因子：
1.4
通讯作者：
Safdar,Amar
中科院分区：
文献类型：
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作者：
Safdar,Amar
了解真菌的发病机制和宿主-病原体在感染的各个阶段的免疫相互作用是检验增强抗真菌免疫防御策略的关键。重组骨髓生长因子，尤其是粒细胞-巨噬细胞集落刺激因子和主要的T辅助（Th） 1细胞因子干扰素-γ，是难治性侵袭性曲霉病患者最常使用的药物。这些细胞因子可单独或联合使用，也可用于接受供体粒细胞输注的中性粒细胞减少症患者。近年来，一些研究者就常规抗真菌药物对宿主免疫应答的辅助作用和病原体抗真菌免疫防御的易感性等方面提出了令人振奋的数据。抗真菌免疫疗法及其在曲霉病治疗中的改善作用将需要临床试验：1)考虑特征明确的真菌疾病；2)阐明潜在的免疫缺陷（如Th1 vs Th2， vs Th17以及自然杀伤细胞和效应清除细胞的功能状态）；3)纳入更具体的患者群体；4)纳入规范的抗真菌药物治疗；重要的是考虑其对宿主免疫反应的影响以及病原体的易感性和毒力的变化。目前，免疫治疗仅用于危及生命的侵袭性真菌疾病患者，这些患者的常规抗真菌药物治疗失败，或晚期真菌疾病患者，以及与常规治疗失败率高相关的因素。
Understanding fungal pathogenesis and host-pathogen immune interaction at various stages of infection is critical to examine strategies for bolstering antifungal immune defenses. Recombinant myeloid growth factors, especially granulocyte-macrophage colony-stimulating factor and the protagonist T helper (Th) 1 cytokine, interferon-γ, are most frequently used in patients with refractory invasive aspergillosis. These cytokines are given alone or in combination and have also been used together in neutropenic patients receiving donor granulocyte transfusions. Recently, a number of investigators have presented provoking data regarding auxiliary effect of conventional antifungal drugs on hosts’ immune response and pathogen’s susceptibility for antifungal immune defenses. Antifungal immunotherapy and its ameliorative role in treatment forAspergillusdisease will need clinical trials that 1) consider well-characterized fungal disease; 2) illustrate underlying immune defect(s) (such as Th1 vs Th2, vs Th17 and functional status of natural killer and effector scavenger cells); 3) include a more specific patient population; 4) include standardized antifungal drug therapy; and importantly 5) consider its impact on hosts’ immune response and changes in pathogen’s susceptibility and virulence. At present, immunotherapy is reserved for patients with life-threatening invasive fungal disease in whom conventional antifungal drug therapy has failed, or for patients with advanced fungal disease and with factors associated with high probability of failure of conventional therapy alone.