Yanagihara K, Tomono K, Sawai T, Hirakata Y, Kadota J, Koga H, Tashiro T, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Am J Respir Crit Care Med. 1997 Jan;155(1):337-42. doi: 10.1164/ajrccm.155.1.9001333.
In a newly established murine model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse panbronchiolitis (DPB), we investigated the effect of oral administration of clarithromycin on lymphocyte accumulation in the lung. Infection was produced by placement of a plastic tube precoated with P. aeruginosa in the bronchus. The number of bacteria on the tube was 6.25 +/- 0.22 log10 colony-forming units (cfu)/ml. Viable bacteria were constantly isolated at 10(5) to 10(6) cfu/specimen from the lungs for more than 1 yr. The histopathologic features resembled those of DPB consisting of massive accumulation of lymphocytes in the lung. The total number of pulmonary lymphocytes started to increase on Day 7, reaching a peak level within 12 d of intratracheal challenge. The number remained steady at that level for up to 120 d. There was also a steady fall in the CD4+/CD8+ ratio in the lungs, commencing on Day 7 and persisting to Day 120. A 10-d course of oral clarithromycin (10 mg/kg/d) from Day 7 resulted in a reduction of lymphocyte numbers to baseline level, although the dose did not influence the number of bacteria in the lungs. Treatment also increased the CD4+/CD8+ ratio to the baseline level from Day 7 to 17. Our results were similar to those detected in bronchoalveolar lavage fluid of patients with DPB and suggest that the therapeutic benefits of clarithromycin are due to its anti-inflammatory properties rather than antimicrobial effect.
在一种新建立的模仿弥漫性泛细支气管炎（DPB）的慢性铜绿假单胞菌呼吸道感染小鼠模型中，我们研究了口服克拉霉素对肺内淋巴细胞积聚的影响。通过将预先涂有铜绿假单胞菌的塑料管放置在支气管中来引发感染。管上细菌的数量为6.25±0.22 log10集落形成单位（cfu）/毫升。在超过1年的时间里，从肺中始终能分离出10⁵至10⁶ cfu/标本的活菌。组织病理学特征类似于DPB，表现为肺内淋巴细胞大量积聚。肺淋巴细胞总数在第7天开始增加，在气管内攻击后12天内达到峰值水平。该数量在该水平保持稳定长达120天。肺内CD4⁺/CD8⁺比值也从第7天开始稳步下降，并持续到第120天。从第7天开始给予10天疗程的口服克拉霉素（10毫克/千克/天），尽管该剂量不影响肺内细菌数量，但可使淋巴细胞数量降至基线水平。治疗还使CD4⁺/CD8⁺比值从第7天至第17天升至基线水平。我们的结果与DPB患者支气管肺泡灌洗液中检测到的结果相似，表明克拉霉素的治疗益处归因于其抗炎特性而非抗菌作用。
