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Analysis of chronic respiratory infection by using a newly established murine model chronic respiratory infection with Pseudomonas aeruginosa-The kinetics of cytokines and analysis of the effect of macrolides-

新建立的铜绿假单胞菌慢性呼吸道感染小鼠模型分析慢性呼吸道感染-细胞因子动力学及大环内酯类药物作用分析-

基本信息

批准号：
11670582
负责人：
KOHNO Shigeru
金额：
$ 1.15万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670582/
关键词：
Chronic infection model Pseudomonas aeruginosa Macrolide Cytokine Lymphocyte of lung

项目摘要

We investigated the role of inflammatory cytokines in a mouse model of chronic Pseudomonas aeruginosa infection mimicking diffuse panbronchiolitis (DPB), and determined the effects of macrolide. The concentrations of IL-1β, IL-2, IL-4, IL-5, IFN-γ and TNFα were measured serially in the lungs of mice with experimentally induced chronic respiratory P.aeruginosa infection until 60 days after inoculation. The concentrations of these cytokines during the course of disease were significantly higher than baseline. A 10-day course of oral clarithromycin (10mg/kg/day) from day 7 result in a reduction of lymphocyte numbers to baseline level, although it increased CD4+/CD8 ratio it the baseline level between day7 to day17. Treatment also significantly inhibited the production of IL-1β and TNF α in the lung. Futhermore the treatment from day 90 after inoculation, the results were similar to those of them. Ketolides are a new class of macrolide antibiotics that have been shown to be active against a variety of bacteria including macrolideresistant bacteria and mycobacteria. We examined the effect of ketolide on chronic respiratory P.aeruginosa infection. Although the MIC of ketolide was more than 400 μg/ml. This antibiotics influenced the number of bacteria in the lung compared with treated mice with other macrolides. It was suggested that ketlide may be associated with biofilm rather than antimicrobial effect. For this new antibiotic investigated, not only in vitro MICs and in vivo pharmacokinetic data but also immunological determinations should be provided in the future study.

我们研究了炎症细胞因子在模拟弥漫性泛细支气管炎（DPB）的铜绿假单胞菌慢性感染小鼠模型中的作用，并确定了大环内酯类药物的作用。采用免疫组织化学方法，对实验性慢性呼吸道铜绿假单胞菌感染小鼠肺组织中IL-1β、IL-2、IL-4、IL-5、IFN-γ和TNFα的浓度进行了动态检测，直至接种后60 d。这些细胞因子的浓度在疾病过程中显着高于基线。从第7天开始口服克拉霉素（10 mg/kg/天）10天，导致淋巴细胞数量降至基线水平，尽管其在第7天至第17天期间使CD 4 +/CD 8比值升高至基线水平。给药还显著抑制了肺中IL-1β和TNF α的产生。从接种后90天开始继续处理，结果与上述两种方法相似。酮内酯类是一类新的大环内酯类抗生素，已被证明对多种细菌具有活性，包括大环内酯耐药菌和分枝杆菌。我们研究了酮内酯对慢性呼吸道铜绿假单胞菌感染的影响。虽然酮内酯的MIC大于400 μg/ml。与其他大环内酯类药物治疗的小鼠相比，这种抗生素影响了肺部细菌的数量。提示氯胺酮可能与生物被膜有关，而不是抗菌作用。对于这一新的抗生素研究，不仅在体外MIC和体内药代动力学数据，但也免疫测定应提供在未来的研究。