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-

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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.