Effects of intratracheal instillation of TNF-a on surfactant metabolism

tion of TNF-a on surfactant metabolism. J. Appl. Physiol. 88: 10–16, 2000.—Tumor necrosis factor-a (TNF-a) has been shown to play an integral role in the pathogenesis of the acute respiratory distress syndrome. This disorder is characterized by a deficiency of alveolar surfactant, a surface-active mate-rial that is composed of key hydrophobic proteins and the major lipid disaturated phosphatidylcholine (DSPC). We in-vestigated how TNF-a might alter DSPC content in rat lungs by instilling the cytokine (2.5 µg) intratracheally for 10 min and then assaying parameters of DSPC synthesis and degra-dation in alveolar type II epithelial cells, which produce surfactant. Cells isolated from rats given TNF-a had 26% lower levels of phosphatidylcholine compared with control. TNF-a treatment also decreased the ability of these cells to incorporate [3H]choline into DSPC by 45 % compared wit