Intrapulmonary cytokine accumulation following BAL and the role of endotoxin contamination

Study objectives: BAL induces alveolar inflammation, but its effects on intrapulmonary cytokines and the mechanisms causing inflammation are uncertain. The objectives of this study were: (1) to characterize cytokine response in the lungs to BAL, and (2) to determine whether endotoxin is introduced into the lungs during BAL, which could promote BAL-induced inflammation. Design and methods: We performed two BAL procedures in healthy volunteers separated by 4 (n = 6), 24 (n = 5), or 72 h (n = 3). The initial BAL was performed in the right middle lobe (RML) and the second BAL was performed in the same location and the lingula. Concentrations of interleukin-8 (IL-8), interleukin-1β (IL-1β), and transforming growth factor-β were measured by enzyme-linked immunosorbent assay and tumor necrosis factor-α (TNF-α) bioactivity was determined. Endotoxin contents of saline (10 and 20 mL) infused through bronchoscopes as well as BAL fluids recovered from six subjects were assessed by limulus amebocyte assay. Results: At 4 h after the initial lavage, but not at later times, BAL fluid recovered from the RML contained increased concentrations of IL-8 and IL- 1β, and increased TNF-α bioactivity. BAL fluid recovered from the lingula contained increased concentrations of TNF-α only at 4 h. All BAL samples tested contained detectable endotoxin as did all saline aliquots instilled through bronchoscopes. Conclusions: There is intrapulmonary accumulation of the cytokines TNF-α, IL-8, and IL-1β in the lavaged lung within 4 h after BAL; this accumulation resolves by 24 h. Endotoxin contamination of the lungs during bronchoscopy may contribute to BAL-induced lung inflammation.