title: Immunomodulatory effects of a low-dose clarithromycin-based macrolide solution pressurised metered dose inhaler.
abstract: OBJECTIVE
  The aim of this study was to assess the effects of low-dose clarithromycin, formulated as solution pressurized metered dose inhaler, following deposition on the Calu-3 respiratory epithelial cells.
  
  
  METHODS
  Clarithromycin was deposited on the air-interface culture of Calu-3 cells using a modified Andersen cascade impactor. Transport of fluorescein-Na, production of mucus and interleukin-8 release from Calu-3 cells following stimulation with transforming growth factor-β and treatment with clarithromycin was investigated.
  
  
  RESULTS
  The deposition of clarithromycin had significant effect on the permeability of fluorescein-Na, suggesting that the barrier integrity was improved following a short-term treatment with clarithromycin (apparent permeability values were reduced to 3.57 × 10(-9) ± 2.32 × 10(-9) cm.s(-1), compared to 1.14 × 10(-8) ± 4.30 × 10(-8) cm.s(-1) for control). Furthermore, the amount of mucus produced was significantly reduced during the course of clarithromycin treatment. The concentration of interleukin-8 secreted from Calu-3 cells following stimulation with transforming growth factor-β resulted in significantly lower level of interleukin-8 released from the cells pre-treated with clarithromycin (5.2 ± 0.5 ng.ml(-1) clarithromycin treated vs. 7.7 ± 0.8 ng.ml(-1) control, respectively).
  
  
  CONCLUSIONS
  Our data demonstrate that treatment with clarithromycin decreases the paracellular permeability of epithelial cells, mucus secretion and interleukin-8 release and therefore, inhaled clarithromycin holds potential as an anti-inflammatory therapy.
authors.affiliation: Respiratory Technology Woolcock Institute of Medical Research and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Mehra
authors.initials: M
authors.lastname: Haghi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Saadat
authors.forename: Bing
authors.initials: B
authors.lastname: Zhu
authors.forename: Gaia
authors.initials: G
authors.lastname: Colombo
authors.forename: Gregory
authors.initials: G
authors.lastname: King
authors.forename: Paul M
authors.initials: PM
authors.lastname: Young
authors.forename: Daniela
authors.initials: D
authors.lastname: Traini
mesh_terms: D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D017291:Clarithromycin / Q000008:administration & dosage* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004867:Equipment Design; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D036501:Metered Dose Inhalers; D009093:Mucus / Q000378:metabolism; D010539:Permeability; D019999:Pharmaceutical Solutions; D011312:Pressure; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D007155:Immunologic Factors; D016209:Interleukin-8; D019999:Pharmaceutical Solutions; D017291:Clarithromycin