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Increased CD8 T ‐cell granzyme B in COPD is suppressed by treatment with low‐dose azithromycin
Author(s) -
Hodge Sandra,
Hodge Greg,
Holmes Mark,
Jersmann Hubertus,
Reynolds Paul N.
Publication year - 2015
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12415
Subject(s) - medicine , granzyme b , granzyme , immunology , azithromycin , peripheral blood mononuclear cell , cd8 , granzyme a , cytotoxic t cell , copd , t cell , immune system , biology , in vitro , microbiology and biotechnology , perforin , antibiotics , biochemistry
Background and objective Corticosteroid resistance in chronic obstructive pulmonary disease ( COPD ) is a major challenge. We have reported increased bronchial epithelial cell apoptosis and increased airway CD8 T ‐cell numbers in COPD . Apoptosis can be induced via the serine protease, granzyme B . However, glucocorticosteroids fail to adequately suppress granzyme B production by CD8 T cells. We previously showed that low‐dose azithromycin reduced airways inflammation in COPD subjects and we hypothesized that it would also reduce granzyme B production by CD8 T cells. 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 We provide further evidence for the application of low‐dose azithromycin as an attractive adjunct treatment option for controlling epithelial cell apoptosis, abnormal airway repair and chronic inflammation in COPD .