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首页> 外文期刊>Infection and immunity >Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.
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Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.

机译：粒细胞集落刺激因子和γ干扰素预防皮质类固醇诱导的对人多形核白细胞诱导的烟曲霉菌丝的损伤的抑制。

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摘要

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.
机译：中性粒细胞（PMN）是抵抗烟曲霉感染的关键防​​御线。在接受皮质类固醇激素治疗的患者中观察到侵袭性曲霉病发生率增加，表明这些化合物对PMN抗真菌功能产生有害作用。为了研究该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，氢化可的松（HCS）和地塞米松（DXS）对PMN诱导的曲霉菌损害的影响在使用或不使用G-CSF和IFN-γ预处理PMN的情况下，研究了烟熏菌丝。在2小时比色四氮唑代谢测定（使用甲硫基四氮唑）中，用HCS（>或= 3,000 microM）或DXS（>或= 10 microM）处理的PMN显示出抑制的菌丝百分率（P <0.02）。此外，HCS（>或= 30 microM）和DXS（>或= 1 microM）均显着抑制了氧化性爆裂，该爆裂是PMN响应调理和非调理菌丝以及N-甲酰基甲硫酰基亮氨酰苯丙氨酸而释放的超氧阴离子所测得的。用G-CSF（4,000 U / ml）和/或IFN-γ（100和1,000 U / ml）预处理PMN 90分钟可防止抑制存在HCS（3,000 microM; P <0.01 ）或DXS（10 microM; P <或= 0.001）。与单独使用IFN-γ相比，G-CSF（4,000 U / ml）和IFN-γ（100 U / ml）的组合对增加HCS处理但不与DXS处理的PMN的抗真菌活性具有加和作用（P = 0.015 ）。因此，这些发现表明，皮质类固醇可响应烟曲霉而损害PMN功能，而G-CSF和IFN-γ可阻止这种损害。

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