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Pathogenesis of septic shock in Pseudomonas aeruginosa pneumonia
Open accessAbstract
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.
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“An experimental study of rabbits with severe Pseudomonas pneumonia and systemic sepsis provided definitive evidence that TNF instilled into the lungs could pass into the systemic circulation, providing direct communication between the lungs and the bloodstream (80).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [80]
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Metadata
- Authors
- Kurahashi, K., Kajikawa, O., Sawa, T., Ohara, M., Gropper, M. A., Frank, D. W., Martin, T. R., & Wiener-Kronish, J. P.
- Affiliations
- University of California, San Francisco (US)
- University of Washington (US)
- Medical College of Wisconsin (US)
- Corresponding author
- Wiener-Kronish, Jeanine P.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1999-09-15
- Volume
- 104
- Issue
- 6
- Pages
- 743-750
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408437
- OpenAlex
- W2087967484
- Cited by
- 316
- References
- 36
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 9 · 2021: 8 · 2020: 7 · 2019: 4 · 2018: 7 · 2017: 11 · 2016: 14 · 2015: 14 · 2014: 18 · 2013: 8 · 2012: 16
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL49810, HL-59239, R01HL059239, R01HL049810)
- National Institute of General Medical Sciences (P01GM037696)
- National Institute of Allergy and Infectious Diseases (AI31665)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- septic shock, Pseudomonas aeruginosa pneumonia, type III secretion system, alveolar epithelial injury, TNF-α, IL-10, bacteremia, systemic inflammatory response, rabbit model
- MeSH terms
- Animals, Cell Line, Humans, Male, Pseudomonas aeruginosa, Pseudomonas Infections, Rabbits, Recombinant Proteins, Shock, Septic, Tumor Necrosis Factor-alpha, Interleukin-10, Pneumonia, Bacterial
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