Low-dose clarithromycin therapy modulates Th17 response in non-cystic fibrosis bronchiectasis patients

Lung. 2014 Dec;192(6):849-55. doi: 10.1007/s00408-014-9619-0. Epub 2014 Jul 14.

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). 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Gas Analysis
  • Breath Tests
  • Bronchiectasis / drug therapy*
  • Bronchiectasis / immunology*
  • Bronchiectasis / pathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Clarithromycin / administration & dosage*
  • Cohort Studies
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / pathology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-17 / metabolism
  • Male
  • Middle Aged
  • Respiratory Function Tests
  • Risk Assessment
  • Sampling Studies
  • Severity of Illness Index
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Treatment Outcome

Substances

  • Interleukin-17
  • Clarithromycin