title: Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial.
abstract: Neutrophilic inflammation plays a causal role in Chronic Obstructive Pulmonary Disease (COPD). Neutrophil derived myeloperoxidase(MPO) matrix metalloproteinases(MMP's), and elastases are thought to contribute to the perpetuation of the disease. The tetracycline analogue doxycycline has been shown to inhibit neutrophil-mediated inflammation. It was thus reasoned that doxycycline may attenuate neutrophil-mediated inflammation in COPD.
  
  
  METHODS
  In this double blind randomized controlled trial the effect of a 3-week course of doxycycline on sputum and systemic inflammatory parameters was evaluated in stable COPD patients. In order to exclude inflammation by bacterial colonisation patients must have 2 negative sputum cultures in the previous year. The effect of doxycycline treatment on inflammatory markers (TNF-α, IL-1β and IL-6) and neutrophil specific markers in sputum (MPO, MMP's, and IL-8) and serum C-reactive protein was evaluated. Sputum was obtained by sputum induction with hypertonic saline.
  
  
  RESULTS
  A total of 41 patients were included. Ten patients were excluded as they were not able to produce sputum at the first or second visit. Baseline characteristics were similar in the two groups. In the remaining patients doxycycline did not influence sputum MPO concentrations. Also MMP-8 and 9, IL-6 and IL-8 concentrations as well as lung function parameters were not affected by doxycycline. Systemic inflammation by means of CRP was also not influenced by doxycycline.
  
  
  CONCLUSIONS
  A three week course of doxycycline did not influence MPO sputum levels nor any of the other inflammatory sputum and systemic markers.
  
  
  BACKGROUND
  ClinicalTrials.gov; No.: NCT00857038 URL: clinicaltrials.gov.
authors.affiliation: Department Pulmonary Diseases, Medical Centre Alkmaar, Alkmaar, The Netherlands.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Prins
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Johannes M A
authors.initials: JM
authors.lastname: Daniels
authors.affiliation: Department of Vascular Surgery, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Lindeman
authors.affiliation: Department of Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; Respiratory Medicine and Experimental Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.affiliation: Department Pulmonary Diseases, Medical Centre Alkmaar, Alkmaar, The Netherlands. Electronic address: W.Boersma@mca.nl.
authors.forename: Wim G
authors.initials: WG
authors.lastname: Boersma
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D013183:Sputum / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D018836:Inflammation Mediators; D002097:C-Reactive Protein; D004318:Doxycycline
keywords: Anti-inflammatory effect; COPD; Doxycycline; Inflammation