title: CCL18 as an indicator of pulmonary fibrotic activity in idiopathic interstitial pneumonias and systemic sclerosis.
abstract: OBJECTIVE
  In diffuse parenchymal lung diseases, the evolution of pulmonary fibrosis is often devastating and may result in death. In this study the role of CCL18 as a biomarker of disease activity in idiopathic interstitial pneumonias (IIPs) and systemic sclerosis (SSc) with lung involvement was evaluated.
  
  
  METHODS
  CCL18 was assessed in supernatants of cultured bronchoalveolar lavage (BAL) cells as well as BAL fluid and serum samples from 43 patients with IIPs, 12 patients with SSc, and 23 healthy control subjects. Concentrations of CCL18 were measured by enzyme-linked immunosorbent assay, and expression of CCL18 was assessed by flow cytometry.
  
  
  RESULTS
  CCL18 concentrations were statistically significantly increased in all patients with fibrotic lung diseases. Spontaneous CCL18 production by BAL cells was negatively correlated with total lung capacity and the diffusion capacity for carbon monoxide, whereas there was a positive correlation of CCL18 concentrations with BAL neutrophil and eosinophil cell counts. Flow cytometry revealed an increase in the percentage of CCL18-positive alveolar macrophages and an increase in the CCL18 fluorescence intensity per cell in patients with fibrotic lung diseases. In a cohort of patients who were followed up for at least 6 months (n = 40), a close negative correlation was observed between changes in the predicted total lung capacity and changes in CCL18 serum concentrations.
  
  
  CONCLUSIONS
  These findings suggest that CCL18 production by BAL cells and serum CCL18 concentrations reflect pulmonary fibrotic activity in patients with IIPs and those with SSc. Monitoring changes in CCL18 production might be an extraordinarily useful tool in clinical practice and in studies aimed at evaluating new approaches for treatment of fibrotic lung diseases.
authors.affiliation: University Hospital Freiburg, Freiburg, Germany. prasse@medizin.ukl.uni-freiburg.de
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Pechkovsky
authors.forename: Galen B
authors.initials: GB
authors.lastname: Toews
authors.forename: Markus
authors.initials: M
authors.lastname: Schäfer
authors.forename: Stephan
authors.initials: S
authors.lastname: Eggeling
authors.forename: Corinna
authors.initials: C
authors.lastname: Ludwig
authors.forename: Martin
authors.initials: M
authors.lastname: Germann
authors.forename: Florian
authors.initials: F
authors.lastname: Kollert
authors.forename: Gernot
authors.initials: G
authors.lastname: Zissel
authors.forename: Joachim
authors.initials: J
authors.lastname: Müller-Quernheim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C111792:CCL18 protein, human; D019742:Chemokines, CC