Faculty Collaboration Database

Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia. J Clin Invest 1999 Sep;104(6):743-50

Date

09/24/1999

Pubmed ID

10491409

Pubmed Central ID

PMC408437

DOI

10.1172/JCI7124

Scopus ID

2-s2.0-0032699215 (requires institutional sign-in at Scopus site)   286 Citations

Abstract

The pathogenesis of septic shock occurring after Pseudomonas aeruginosa pneumonia was studied in a rabbit model. The airspace instillation of the cytotoxic P. aeruginosa strain PA103 into the rabbit caused a consistent alveolar epithelial injury, progressive bacteremia, and septic shock. The lung instillation of a noncytotoxic, isogenic mutant strain (PA103DeltaUT), which is defective for production of type III secreted toxins, did not cause either systemic inflammatory response or septic shock, despite a potent inflammatory response in the lung. The intravenous injection of PA103 did not cause shock or an increase in TNF-alpha, despite the fact that the animals were bacteremic. The systemic administration of either anti-TNF-alpha serum or recombinant human IL-10 improved both septic shock and bacteremia in the animals that were instilled with PA103. Radiolabeled TNF-alpha instilled in the lung significantly leaked into the circulation only in the presence of alveolar epithelial injury. We conclude that injury to the alveolar epithelium allows the release of proinflammatory mediators into the circulation that are primarily responsible for septic shock. Our results demonstrate the importance of compartmentalization of inflammatory mediators in the lung, and the crucial role of bacterial cytotoxins in causing alveolar epithelial damage in the pathogenesis of acute septic shock in P. aeruginosa pneumonia.

Author List

Kurahashi K, Kajikawa O, Sawa T, Ohara M, Gropper MA, Frank DW, Martin TR, Wiener-Kronish JP

Author

Dara W. Frank PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Line
Humans
Interleukin-10
Male
Pneumonia, Bacterial
Pseudomonas Infections
Pseudomonas aeruginosa
Rabbits
Recombinant Proteins
Shock, Septic
Tumor Necrosis Factor-alpha