EFFECT OF CLARITHROMYCIN ON LYMPHOCYTES IN CHRONIC RESPIRATORY PSEUDOMONAS-AERUGINOSA INFECTION

In a newly established murine model of chronic Pseudomonas aeruginosa respiratory infection mimicking diffuse panbronchiolitis (DPB), we inv estigated the effect of oral administration of clarithromycin on lymph ocyte accumulation in the lung. Infection was produced by placement of a plastic tube precoated with P. aeruginosa in the bronchus. The numb er of bacteria on the tube was 6.25 +/- 0.22 logic colony-forming unit s (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 f eatures resembled those of DPB consisting of massive accumulation of l ymphocytes in the lung. The total number of pulmonary lymphocytes star ted to increase on Day 7, reaching a peak level within 12 d of intratr acheal challenge. The number remained steady at that level for up to 1 20 d. There was also a steady fall in the CD4(+)/CD8(+) ratio in the l ungs, 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 influ ence the number of bacteria in the lungs. Treatment also increased the CD4(+)/CD8(+) ratio to the baseline level from Day 7 to 17. Our resul ts were similar to those detected in bronchoalveolar lavage fluid of p atients with DPB and suggest that the therapeutic benefits of clarithr omycin are due to its anti-inflammatory properties rather than antimic robial effect.