title: Increased levels of soluble interleukin-6 receptor and CCL3 in COPD sputum.
abstract: BACKGROUND
  COPD patients have increased numbers of macrophages and neutrophils in the lungs. Interleukin-6 (IL-6) trans-signaling via its soluble receptor sIL-6R, governs the influx of innate immune cells to inflammatory foci through regulation of the chemokine CCL3. We hypothesized that there would be enhanced levels of IL-6, sIL-6R and CCL3 in COPD sputum.
  
  
  METHODS
  59 COPD patients, 15 HNS and 15 S underwent sputum induction and processing with phosphate buffered saline to obtain supernatants for IL-6, sIL-6R and CCL3 analysis. Cytoslides were produced for differential cell counting and immunocytochemistry (COPD; n = 3) to determine cell type surface expression of the CCL3 receptors CCR5 and CCR1.
  
  
  RESULTS
  COPD patients expressed higher levels (p < 0.05) of sIL-6R and CCL3 compared to controls (sIL-6R medians pg/ml: COPD 166.4 vs S 101.1 vs HNS 96.4; CCL3 medians pg/ml: COPD 117.9 vs S 0 vs HNS 2.7). COPD sIL-6R levels were significantly correlated with sputum neutrophil (r = 0.5, p < 0.0001) and macrophage (r = 0.3, p = 0.01) counts. Immunocytochemical analysis revealed that CCR5 and CCR1 were exclusively expressed on airway macrophages.
  
  
  CONCLUSIONS
  Enhanced airway generation of sIL-6R may promote IL-6 trans-signaling in COPD. Associated upregulation of CCL3 may facilitate the recruitment of macrophages into the airways by ligation of CCR1 and CCR5.
authors.forename: Arjun K
authors.initials: AK
authors.lastname: Ravi
authors.forename: Shruti
authors.initials: S
authors.lastname: Khurana
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lemon
authors.forename: Jonathan
authors.initials: J
authors.lastname: Plumb
authors.forename: George
authors.initials: G
authors.lastname: Booth
authors.forename: Louise
authors.initials: L
authors.lastname: Healy
authors.forename: Matthew
authors.initials: M
authors.lastname: Catley
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D054405:Chemokine CCL3 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000378:metabolism*; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis*; D013183:Sputum / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D019947:Receptors, Interleukin-6