CCL18 in serum, BAL fluid and alveolar macrophage culture supernatant in interstitial lung diseases

Respir Med. 2013 Sep;107(9):1444-52. doi: 10.1016/j.rmed.2013.06.004. Epub 2013 Jul 5.


Background: CCL18 is a CC chemokine produced mainly by antigen-presenting cells, and is chemotactic predominantly for T-lymphocytes. CCL18 can stimulate pulmonary fibroblasts and increase the collagen production in vitro.

Objectives: This study aimed to compare the CCL18 levels in a variety of human biological fluids between various interstitial lung diseases (ILDs), and to reveal potential correlations with BAL cell differentials.

Methods: Serum and bronchoalveolar lavage fluid (BALF) samples were collected from 199 patients with idiopathic pulmonary fibrosis (IPF), idiopathic non-specific interstitial pneumonia (iNSIP), respiratory bronchiolitis interstitial lung disease/desquamative interstitial pneumonia (RB-ILD/DIP), cryptogenic organizing pneumonia (COP), hypersensitivity pneumonitis (HP) or sarcoidosis. Alveolar macrophage (AM) culture was performed in 44 patients with IPF, iNSIP, COP, HP, sarcoidosis or non-ILDs. The CCL18 levels in serum, BALF and AM culture supernatant were measured with ELISA.

Results: Both serum and BALF CCL18 levels in all ILDs were higher than in controls (all p < 0.005). In HP, CCL18 serum levels were the highest of all ILDs, and its BALF levels were significantly higher than in other ILDs except iNSIP. The BALF CCL18 levels markedly correlated with BAL cell differentials, especially with the percentage of BAL lymphocytes. In AM culture supernatant, the spontaneous CCL18 production was higher in HP and COP than in IPF and controls.

Conclusion: CCL18 levels in serum, BALF and AM culture supernatant are markedly increased in various inflammatory and fibrotic ILDs. However, the CCL18 level being highest in HP among the investigated ILDs suggests that CCL18 may be more profoundly involved in inflammatory immune responses.

Keywords: AM; AMAC; ATS/ERS; AaO(2); American Thoracic Society/European Respiratory Society; BALF; CC chemokine ligand; CCL; CCL18; COP; DC-CK; DIP; DLco; ELISA; FEV; Fibrosis; HP; HRCT; Hypersensitivity pneumonitis; IFN; IIP; IL; ILD; IPF; Idiopathic pulmonary fibrosis; Inflammation; Interstitial lung disease; LPS; MIP; NSIP; PARC; RB-ILD; SaO(2); T-helper; TNF; Th; VC; alternative macrophage activation-associated CC chemokine; alveolar macrophage; alveolar-arterial PO(2) difference; bronchoalveolar lavage fluid; cryptogenic organizing pneumonia; dendritic cell-chemokine; desquamative interstitial pneumonia; diffusing capacity of the lung for carbon monoxide; enzyme-linked immunosorbent assay; forced expiratory volume; high-resolution computed tomography; hypersensitivity pneumonitis; idiopathic interstitial pneumonia; idiopathic pulmonary fibrosis; interferon; interleukin; interstitial lung disease; lipopolysaccharide; monocyte inflammatory protein; non-specific interstitial pneumonia; oxygen percent saturation (arterial); pulmonary and activity-regulated chemokine; respiratory bronchiolitis interstitial lung disease; tumor necrosis factor; vital capacity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Case-Control Studies
  • Cells, Cultured
  • Chemokines, CC / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lung Diseases, Interstitial / metabolism*
  • Macrophages, Alveolar / chemistry*
  • Male


  • CCL18 protein, human
  • Chemokines, CC