| Project/Area Number |
11670582
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Nagasaki University |
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Principal Investigator |
KOHNO Shigeru Nagasaki University, School of Medicine Professor, 大学院・医学研究科, 教授 (80136647)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGIHARA Katsunori Nagasaki University, School of Medicine Assistant, 医学部・附属病院, 助手 (40315239)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2000: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Chronic infection model / Pseudomonas aeruginosa / Macrolide / Cytokine / Lymphocyte of lung |
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| Research Abstract |
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.
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