Elevated levels of MCP-1, MIP-alpha and MIP-1 beta in the bronchoalveolar lavage (BAL) fluid of patients with mustard gas-induced pulmonary fibrosis

Toxicology. 2007 Oct 30;240(1-2):60-9. doi: 10.1016/j.tox.2007.07.014. Epub 2007 Aug 1.

Abstract

Objective: Role of chemokines in the pathogenesis of pulmonary fibrosis (PF) due to sulfur mustard (SM) gas inhalation.

Patients: 18 veterans with SM gas-induced PF, 15 patients with IPF and 18 normal as controls.

Intervention: Chest roentgenograms, PFTs, the percentage DLCO, high-resolution CT scans of the chest, and analyses of BAL fluids for chemokines (MCP-1, MIP-1 alpha, and MIP-1 beta) were performed in all cases.

Results: There were significant differences in chemokines (MCP-1, MIP-1 alpha, and MIP-1 beta) levels of BAL fluid between patients with PF and healthy controls (p<0.0006). MCP-1 and MIP-1 alpha levels in BAL fluid correlate only with the percentage and the absolute number lymphocytes of the BAL fluid in patients with PF due to SM gas inhalation (p=0.0006/p=0.03; p=0.04/p=0.02; respectively). The BAL fluid level of MIP-alpha in SM gas-induced PF was significantly correlated with the number of lymphocytes (r=-0.56, p=0.01), neutrophils (r=-0.50, p=0.03) and eosinophils (r=-0.49, p=0.03). A significant negative correlation was observed between the percentage of Dlco and MCP-1 and MIP-1 alpha levels in BAL fluid in patients with PF (r=-0.65, p=0.003; r=-0.48, p=0.04; respectively).

Conclusion: Neutrophils alveolitis, presence of eosinophils, and higher concentrations of interleukin MCP-1, MIP-1 alpha, and MIP-1 beta in BAL fluid are associated with the development of fibrosis in SM victims.

MeSH terms

  • Adult
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • Case-Control Studies
  • Cell Count
  • Chemical Warfare Agents / toxicity*
  • Chemokine CCL2 / analysis*
  • Chemokine CCL2 / immunology
  • Chemokine CCL3 / analysis*
  • Chemokine CCL3 / immunology
  • Chemokine CCL4 / analysis*
  • Eosinophils / cytology
  • Humans
  • Lymphocytes / cytology
  • Macrophages, Alveolar / cytology
  • Mustard Gas / toxicity*
  • Neutrophils / cytology
  • Pulmonary Fibrosis / chemically induced*
  • Pulmonary Fibrosis / immunology

Substances

  • CCL2 protein, human
  • CCL3 protein, human
  • CCL4 protein, human
  • Chemical Warfare Agents
  • Chemokine CCL2
  • Chemokine CCL3
  • Chemokine CCL4
  • Mustard Gas