Endogenous tumor necrosis factor (TNF) alpha mediates neutrophil accumulation at the mid-phase of a murine model of Pseudomonas aeruginosa pneumonia.

ABSTRACT

To determine the role of endogenous tumor necrosis factor (TNF) alpha on neutrophil influx into the lungs in acute Pseudomonas aeruginosa pneumonia, we evaluated TNF alpha activity, inflammatory cell response and neutrophil chemotactic activity in the bronchoalveolar lavage fluids (BALFs) of P. aeruginosa-infected mice. In the case of fatal pneumonia, the TNF alpha activity in the BALFs appeared within 3 hr, peaked at 6-12 hr and attenuated within 24 hr after intratracheal challenging, while no TNF alpha activity was detected in the plasma. The elevation of TNF alpha activity in the BALFs was closely associated with neutrophil accumulation. Mirroring the TNF alpha activity response and the influx of neutrophils into the murine airway, the number of neutrophils in the BALFs increased within 3 hr, peaked at 6-12 hr and remained elevated up to 24 hr after challenging. Neutralization of the TNF alpha activity in the BALFs with anti-murine TNF antiserum decreased the level of neutrophil migration by BALF 45.0-49.7% at 6 hr and 49.3-54.2% at 12 hr, while the neutralizing antiserum had no effect on the level of neutrophil migration by BALFs at 3 and 24 hr. Furthermore, the intravenous administration of anti-murine TNF antiserum 2 hr before challenging significantly inhibited neutrophil migration into the lungs of mice with sublethal pneumonia (P < 0.05; compared with mice receiving pre-immune serum). These data suggest that intra-alveolar TNF alpha plays an important role in causing lung neutrophil accumulation at the mid-phase of murine P. aeruginosa pneumonia.