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Low-Dose Clarithromycin Therapy Modulates Th17 Response In Non-Cystic Fibrosis Bronchiectasis Patients

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Abstract

Introduction

Th17 cells play a crucial role in neutrophilic inflammation and tissue injury in non-cystic fibrosis (non-CF) bronchiectasis. Clarithromycin demonstrates anti-inflammatory and immunomodulatory properties but the effect of long-term clarithromycin prophylaxis on the Th17 response in non-CF bronchiectasis is still unexplored.

Methods

Th17 response was studied in 22 patients with stable non-CF bronchiectasis receiving daily 500-mg clarithromycin for 12 weeks. We analysed IL-17 concentrations in exhaled breath condensate (EBC) and peripheral blood Th17 cells, whereas functional parameters and clinical data were recorded in parallel.

Results

Both, post-treatment absolute counts of CD4+IL17+ cells in peripheral blood and IL-17 levels in EBC decreased significantly (post-treatment CD4+IL17+ mean 2.418 ± 0.414 cells/μl versus pre-treatment 3.202 ± 0.507 cells/μl, p = 0.036 and post-treatment IL-17 mean levels 7.16 ± 0.47 pg/ml versus pre-treatment 9.32 ± 0.47 pg/ml, p < 0.001, respectively). Post-treatment EBC IL-17 levels decreased significantly in both patients who exhibited exacerbations and those who remained stable during the study period (mean 6.72 ± 0.37 versus 9.12 ± 0.64 pg/ml, p = 0.01 and 7.69 ± 0.9 versus 9.53 ± 0.72 pg/ml, p = 0.042, respectively), while pre-treatment and post-treatment levels did not differ between the two groups (p = 0.665 and p = 0.465, respectively). PaO2 improved significantly (post-treatment mean 77.73 ± 2.23 mmHg versus pre-treatment 73.18 ± 2.22 mmHg, p = 0.025), while PaCO2, post-bronchodilation FEV1, and post-bronchodilation FVC remained unaltered.

Conclusions

Our results argue for a reduction of both systemic and local Th17 response after prophylactic, low-dose clarithromycin administration in patients with non-CF bronchiectasis, suggestive of a potential anti-inflammatory and/or immunomodulatory action.

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Acknowledgments

Dr. Fouka has received grant support over the past 3 years from the Hellenic Thoracic Society to perform research on the immunomodulating effects of clarithromycin on patients with bronchiectasis using exhaled breath condensate. All authors also confirm that the manuscript is not under consideration by any other publication.

Conflict of interest

All authors accept direct responsibility for the manuscript and declare no financial or other relative conflict of interest.

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Correspondence to Evangelia Fouka.

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Fouka, E., Lamprianidou, E., Arvanitidis, K. et al. Low-Dose Clarithromycin Therapy Modulates Th17 Response In Non-Cystic Fibrosis Bronchiectasis Patients. Lung 192, 849–855 (2014). https://doi.org/10.1007/s00408-014-9619-0

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  • DOI: https://doi.org/10.1007/s00408-014-9619-0

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