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

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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 (DLCO), high-resolution CT scans of the chest, and analyses of BAL fluids for five cytokines interleukin-8 (IL-8), IL-1β, IL-6, tumor necrosis factor-α (TNF-α), IL-12, and the growth factors transforming growth factor-β (TGF-β), 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-1β, IL-6, TNF-α, IL-12) levels of BAL fluid between patients with PF and healthy controls. TGF-β, 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 DLCO 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 DLCO and TGF-β (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 DLCO% and the other BAL cells. Of all measured cytokines and growth factors, only IL-8 and TGF-β 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.