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侵袭性曲霉病的小鼠模型:体外和体内条件下给予γ干扰素的不同益处。

A murine model of invasive aspergillosis: variable benefit of interferon-gamma administration under in vitro and in vivo conditions.

作者信息

Johnson Christopher P, Edmiston Charles E, Zhu Yong-Ran, Adams Mark B, Roza Allan M, Kurup Viswanath

机构信息

Division of Transplant Surgery, Medical College of Wisconsin and Zablocki Veterans Medical Center, Milwaukee, Wisconsin 53226, USA.

出版信息

Surg Infect (Larchmt). 2005 Winter;6(4):397-407. doi: 10.1089/sur.2005.6.397.

DOI:10.1089/sur.2005.6.397
PMID:16433604
Abstract

BACKGROUND

Interferon-gamma modulates host defense in a number of infectious diseases. Previous studies have shown that systemic administration of interferon-gamma (IFN-gamma) can enhance survival in experimental invasive aspergillosis (IA).

METHODS

Using a novel model of murine IA that is characterized by primary pulmonary infection, we investigated the role of IFN-gamma in the phagocytosis and killing of Aspergillus fumigatus by murine neutrophils and pulmonary alveolar macrophages in vitro and the impact of systemic and regional administration of IFN-gamma on the course of IA in glucocorticoid-treated mice.

RESULTS

In vitro, IFN-gamma significantly enhanced phagocytosis and killing function of both neutrophils and alveolar macrophages from normal animals, but not cortisone-treated animals. In vivo, intravenous administration of IFN-gamma did not improve phagocyte recruitment, in vivo killing, or mortality from IA. Regional (intranasal) administration of IFN-gamma to the lungs enhanced recruitment of phagocytic cells to the lungs and improved in vivo killing, but did not alter (and actually worsened) mortality from IA.

CONCLUSIONS

The in vitro and in vivo effects of IFN-gamma in IA are contingent on many variables, including the route of administration and the specific pathogenesis of infection.

摘要

背景

γ干扰素在多种传染病中调节宿主防御。先前的研究表明,全身给予γ干扰素(IFN-γ)可提高实验性侵袭性曲霉病(IA)的生存率。

方法

使用一种以原发性肺部感染为特征的新型小鼠IA模型,我们研究了IFN-γ在体外对小鼠中性粒细胞和肺泡巨噬细胞吞噬和杀灭烟曲霉的作用,以及全身和局部给予IFN-γ对糖皮质激素治疗小鼠IA病程的影响。

结果

在体外,IFN-γ显著增强正常动物中性粒细胞和肺泡巨噬细胞的吞噬和杀伤功能,但对可的松治疗的动物无此作用。在体内,静脉注射IFN-γ并不能改善吞噬细胞的募集、体内杀伤或IA导致的死亡率。对肺部进行局部(鼻内)给予IFN-γ可增强吞噬细胞向肺部的募集并改善体内杀伤,但并未改变(实际上还恶化了)IA导致的死亡率。

结论

IFN-γ在IA中的体外和体内作用取决于许多变量,包括给药途径和感染的具体发病机制。

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Exogenous interferon-alpha and interferon-gamma increase lethality of murine inhalational anthrax.
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