Roilides E, Uhlig K, Venzon D, Pizzo P A, Walsh T J
Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892.
Infect Immun. 1993 Nov;61(11):4870-7. doi: 10.1128/iai.61.11.4870-4877.1993.
Neutrophils (PMNs) are a critical line of defense against Aspergillus fumigatus infection. Increased frequency of invasive aspergillosis has been observed in patients receiving corticosteroids, suggesting a deleterious effect of these compounds on PMN antifungal function. To investigate this hypothesis and to determine the potential preventive utility of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma), the effects of hydrocortisone (HCS) and dexamethasone (DXS) on PMN-induced damage of Aspergillus fumigatus hyphae were studied with or without pretreatment of PMNs with G-CSF and IFN-gamma. PMNs treated with HCS (> or = 3,000 microM) or DXS (> or = 10 microM) during a 2-h colorimetric tetrazolium metabolic assay (using methylthiotetrazolium) showed suppressed percentage of hyphal damage (P < 0.02). In addition, both HCS (> or = 30 microM) and DXS (> or = 1 microM) significantly suppressed oxidative burst measured as superoxide anion release by PMNs in response to opsonized and nonopsonized hyphae as well as to N-formylmethionyl leucyl phenylalanine. Pretreatment of PMNs with G-CSF (4,000 U/ml) and/or IFN-gamma (100 and 1,000 U/ml) for 90 min prevented the suppression of hyphal damage that occurred in the presence of HCS (3,000 microM; P < 0.01) or DXS (10 microM; P < or = 0.001). G-CSF (4,000 U/ml) and IFN-gamma (100 U/ml) combined had an additive effect on increasing the antifungal activity of HCS-treated but not of DXS-treated PMNs compared with IFN-gamma alone (P = 0.015). Thus, these findings reveal that corticosteroids impair PMN function in response to A. fumigatus and that G-CSF and IFN-gamma prevent this impairment.
中性粒细胞（PMNs）是抵御烟曲霉感染的关键防线。在接受皮质类固醇治疗的患者中，侵袭性曲霉病的发病率有所增加，这表明这些化合物对PMN的抗真菌功能具有有害作用。为了研究这一假设并确定粒细胞集落刺激因子（G-CSF）和γ干扰素（IFN-γ）的潜在预防作用，我们研究了氢化可的松（HCS）和地塞米松（DXS）对PMN诱导的烟曲霉菌丝损伤的影响，同时观察了PMN在使用G-CSF和IFN-γ预处理或未预处理的情况下的变化。在2小时的比色四氮唑代谢试验（使用甲基硫代四氮唑）中，用HCS（≥3000μM）或DXS（≥10μM）处理的PMN显示菌丝损伤百分比受到抑制（P<0.02）。此外，HCS（≥30μM）和DXS（≥1μM）均显著抑制了PMN对调理和未调理的菌丝以及对N-甲酰甲硫氨酰亮氨酰苯丙氨酸的反应中以超氧阴离子释放量衡量的氧化爆发。用G-CSF（4000 U/ml）和/或IFN-γ（100和1000 U/ml）对PMN预处理90分钟可防止在存在HCS（3000μM；P<0.01）或DXS（10μM；P≤0.001）时发生的菌丝损伤抑制。与单独使用IFN-γ相比，G-CSF（4000 U/ml）和IFN-γ（100 U/ml）联合使用对增加HCS处理而非DXS处理的PMN的抗真菌活性具有相加作用（P = 0.015）。因此，这些发现表明皮质类固醇会损害PMN对烟曲霉的反应功能，而G-CSF和IFN-γ可预防这种损害。
