INTRAPORTAL LIPOPOLYSACCHARIDE SUPPRESSES PULMONARY ANTIBACTERIAL DEFENSE-MECHANISMS

Translocation of enteric bacteria or their components (or both) has be en postulated to play a role in precipitating sepsis or the systemic i nflammatory response syndrome, To simulate the effects of translocatio n on pulmonary host defenses, lipopolysaccharide was injected into the portal vein of normal rats that were subsequently challenged by aeros ol inoculation with Pseudomonas aeruginosa, injection of LPS into the portal vein resulted in increased serum tumor necrosis factor (TNF)-al pha levels and reduction in lung clearance of P. aeruginosa after aero sol challenge, There were corresponding reductions in alveolar neutrop hil recruitment, diminished alveolar macrophage phagocytosis and super oxide anion (O-2(-)) production, and diminished lung TNF recovered by bronchoalveolar ravage. Furthermore, prior intravenous injection of re combinant TNF-alpha reproduced the defective bacterial clearance, the altered recruitment of airspace neutrophils, and the defective alveola r macrophage phagocytosis. Thus, systemic TNF-alpha is important in al tering pulmonary defenses, and this work supports the concept that bac terial translocation may adversely affect host defenses in distant org ans.