Roilides E, Blake C, Holmes A, Pizzo P A, Walsh T J
Infectious Diseases Section, National Cancer Institute, Bethesda, MD 20892, USA.
J Med Vet Mycol. 1996 Jan-Feb;34(1):63-9.
Treatment with corticosteroids is an important risk factor for development of invasive aspergillosis. We evaluated the effect of dexamethasone (DEX) on superoxide anion (O2-) release and damage caused by elutriated human monocytes (EHM) on unopsonized hyphae of Aspergillus fumigatus. In addition, we studied the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on these functions of DEX-treated EHM. Treatment of EHM with concentrations of DEX ranging from 5 to 500 nM (1.4-140 ng ml-1) for 48 h suppressed O2- release in response to phorbol myristate acetate in a dose-dependent fashion. Similarly, DEX significantly suppressed hyphal damage caused by EHM as measured by colorimetric MTT assay. Both GM-CSF (5 ng ml-1) and IFN-gamma (1.2 ng ml-1) added at day 0 to the EHM together with DEX (500 nM) significantly enhanced O2- release and percentage hyphal damage, preventing the DEX-induced suppression of EHM function. Thus, GM-CSF and IFN-gamma prevented the deleterious effects of DEX on antifungal activity of EHM against Aspergillus suggesting a potential therapeutic role in patients at risk for or suffering from invasive aspergillosis.
使用皮质类固醇进行治疗是侵袭性曲霉病发生的一个重要危险因素。我们评估了地塞米松（DEX）对经淘洗的人单核细胞（EHM）释放超氧阴离子（O2-）以及对烟曲霉未调理菌丝造成损伤的影响。此外，我们研究了粒细胞-巨噬细胞集落刺激因子（GM-CSF）和干扰素-γ（IFN-γ）对经DEX处理的EHM这些功能的影响。用浓度范围为5至500 nM（1.4 - 140 ng/ml）的DEX处理EHM 48小时，以剂量依赖方式抑制了其对佛波酯肉豆蔻酸酯的O2-释放。同样，通过比色MTT测定法测量，DEX显著抑制了EHM对菌丝造成的损伤。在第0天向EHM中添加GM-CSF（5 ng/ml）和IFN-γ（1.2 ng/ml）以及DEX（500 nM），可显著增强O2-释放和菌丝损伤百分比，防止DEX诱导的EHM功能抑制。因此，GM-CSF和IFN-γ可防止DEX对EHM抗烟曲霉真菌活性的有害影响，提示其在有侵袭性曲霉病风险或患有侵袭性曲霉病的患者中具有潜在治疗作用。
