TUMOR-NECROSIS-FACTOR-ALPHA DECREASES SURFACTANT PROTEIN-B MESSENGER-RNA IN MURINE LUNG

Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfacta nt. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism. Tumor necr osis factor-alpha (TNF-alpha), a primary mediator of acute lung inflam mation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145- 2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody . SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment . Intratracheal murine TNF-alpha also resulted in decreased SP-B and S P-C mRNA levels in the bronchiolar and alveolar epithelium of adult FV B/N mice, as demonstrated by Si nuclease protection and in situ hybrid ization assays, despite minimal histological inflammation. SP-A mRNA w as not significantly altered after anti-CDS antibody and was only mild ly decreased after TNF-alpha. As previously reported, intercellular ad hesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases as sociated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene exp ression may contribute to the surfactant dysfunction and atelectasis o bserved in inflammatory lung diseases.