Related Experiment Videos
Effect of clarithromycin on lymphocytes in chronic respiratory Pseudomonas aeruginosa infection
K Yanagihara1, K Tomono, T Sawai
1Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Abstract:
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.
Insights
Clarithromycin reduced lung lymphocyte accumulation in a chronic Pseudomonas aeruginosa infection model. This suggests its therapeutic benefits in diffuse panbronchiolitis stem from anti-inflammatory, not antimicrobial, actions.
Area of Science:
- Pulmonary Medicine
- Immunology
- Microbiology
Background:
- Chronic Pseudomonas aeruginosa respiratory infection can mimic diffuse panbronchiolitis (DPB).
- DPB is characterized by massive pulmonary lymphocyte accumulation and altered CD4+/CD8+ ratios.
Purpose of the Study:
- To investigate the effect of clarithromycin on lymphocyte accumulation in a murine model of chronic P. aeruginosa respiratory infection.
- To determine if clarithromycin's benefits are due to anti-inflammatory or antimicrobial properties.
Main Methods:
- A murine model of chronic P. aeruginosa respiratory infection was established using a pre-coated plastic tube.
- Pulmonary lymphocyte counts and CD4+/CD8+ ratios were assessed over 120 days.
- Oral clarithromycin (10 mg/kg/d) was administered for 10 days starting on Day 7 post-infection.
Main Results:
- A significant increase in pulmonary lymphocytes and a decrease in the CD4+/CD8+ ratio were observed from Day 7 to 120.
- Clarithromycin treatment reduced lymphocyte numbers to baseline levels and normalized the CD4+/CD8+ ratio.
- Bacterial load in the lungs was not affected by clarithromycin treatment.
Conclusions:
- Clarithromycin exhibits anti-inflammatory effects in chronic P. aeruginosa respiratory infection, reducing pulmonary lymphocyte accumulation.
- The therapeutic benefits of clarithromycin in DPB are likely due to its anti-inflammatory properties rather than its antimicrobial activity.
- This study provides insights into the mechanism of action for clarithromycin in treating DPB-like conditions.