Levels of Cytokine in Bronchoalveolar Lavage (BAL) Fluid in Patients with Pulmonary Fibrosis Due to Sulfur Mustard Gas Inhalation

Abstract

This study was designed to analyze cytokine levels in bronchoalveolar lavage (BAL) fluid of patients with pulmonary fibrosis (PF) and was performed at a University hospital. Nineteen veterans had mustard gas-induced PF, and 19 normal veterans were used as a control group. Chest roentgenograms, pulmonary function tests (PFTs), the percentage diffusing capacity of carbon monoxide (D(LCO)), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-12, and the growth factors transforming growth factor-beta (TGF-beta), insulin-like growth factor-1 (IGF-1), and epidermal growth factor (EGF) were performed in all cases. A transbronchial lung biopsy was done in all patients. There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-beta, EGF, and IGF-1 levels were also significantly increased in patients with PF compared with controls. A significant negative correlation was observed between the percentage of D(LCO) and IL-8 levels in BAL fluid in patients with PF (r = -0.47, p = 0.04). A significant negative correlation was also seen between the percentage of D(LCO) and TGF-beta (r = 0.53, p = 0.02) in these patients. Except for the percentage and the absolute number of the BAL fluid neutrophils (r = 0.70, p = 0.001 and r = -0.62, p = 0.005, respectively), no correlation was found between D(LCO)% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-beta showed a significant correlation with the degree of fibrosis (p = 0.004, p = 0.04). The increased levels of cytokines and growth factors in the BAL fluid suggest the possible causative mechanism in the lung in sulfur mustard gas-induced PF by recruitment of neutrophils and eosinophils into the lung.