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Intrapulmonary Cytokine Accumulation Following BAL and the Role of Endotoxin Contamination^*

^* From the Department of Medicine, Kansas City Veterans Affairs Medical Center (Drs. Nelson, Wesselius, and Ms. Bailey), Kansas City, MO; and the Division of Pulmonary and Critical Care Medicine, University of Kansas School of Medicine (Dr. Wald), Kansas City, KS.

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-1ß (IL-1ß), and transforming growth factor-ß were measured by enzyme-linked immunosorbent assay and tumor necrosis factor- (TNF-) 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-1ß, and increased TNF- bioactivity. BAL fluid recovered from the lingula contained increased concentrations of TNF- 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-, IL-8, and IL-1ß 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.

Key Words: bronchoalveolar lavage • cytokines • endotoxin • inflammation

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