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

• DOI: 10.1007/s00408-014-9619-0
• Publication Date: 2014-07-13T09:14:07Z
• Authors: Evangelia Fouka; Eleftheria Lampri...; Konstantinos Arva...; Eirini Filidou; George Kolios; Paraskevi Miltiades; Emmanouil Paraskakis; Antonios Antoniadis; Ioannis Kotsianidis; Demosthenes Bouros
• Keywords: Adult; Male; Cystic Fibrosis; Dose-Response Relationship, Drug; Interleukin-17; Middle Aged; Risk Assessment; Drug Administration Schedule; Sampling Studies; Bronchiectasis; Respiratory Function Tests; 3. Good health; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Breath Tests; 13. Climate action; Clarithromycin; Humans; Female; Blood Gas Analysis; Bronchoalveolar Lavage Fluid; Aged; Follow-Up Studies

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.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.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). PaO(2) improved significantly (post-treatment mean 77.73 ± 2.23 mmHg versus pre-treatment 73.18 ± 2.22 mmHg, p = 0.025), while PaCO(2), post-bronchodilation FEV1, and post-bronchodilation FVC remained unaltered.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.