학술논문

Increased CD8 T-cell granzyme B in COPD is suppressed by treatment with low-dose azithromycin
Document Type
Academic Journal
Source
Respirology. Jan 01, 2015 20(1):95-100
Subject
Language
English
ISSN
1323-7799
Abstract
BACKGROUND AND OBJECTIVE:: METHODS:: We administered 250 mg azithromycin daily for 5 days then twice weekly (total 12 weeks) to 11 COPD subjects (five current smokers; six ex-smokers) and assessed granzyme B in the airway (bronchoalveolar lavage), intra-epithelial compartment and peripheral blood, collected before and following administration of azithromycin. To then dissect the effects of on CD4 and CD8 T-cell subsets, we applied an in vitro assay and physiologically relevant concentrations of azithromycin (and, for comparison, n-acetyl cysteine) and stimulation of peripheral blood mononuclear cells from five healthy subjects with CD3/CD28 T-cell expander. RESULTS:: T-cell granzyme B production in both airway and intra-epithelial compartments was reduced in COPD patients following 12 weeks of azithromycin treatment, with no significant effect in blood. Both azithromycin and n-acetyl cysteine suppressed CD4 T-cell granzyme B production, but only azithromycin was effective at reducing CD8+ T-cell granzyme B production in vitro. CONCLUSIONS:: SUMMARY AT A GLANCE: In COPD patients, low-dose azithromycin, unlike corticosteroids or n-acetyl cysteine, reduced production of the cytotoxic mediator granzyme B by CD8 T cells from both airway and intra-epithelial compartments. This provides further evidence for the application of azithromycin for controlling epithelial cell apoptosis, abnormal airway repair and chronic inflammation in COPD.