Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Abstract
Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
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TNF is produced during Gram-negative bacteria-induced acute septic shock.
“TNF is produced during Gram-negative bacteria-induced acute septic shock (3).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [3]
TNF is a necessary and sufficient mediator of lethal septic shock caused by infection with Gram-negative bacteria.
“Consider as one example the case of TNF, a cytokine implicated as a necessary and sufficient mediator of lethal septic shock caused by infection with Gram-negative bacteria.”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [3]
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Self-citation
- Authors
- Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A.
- Affiliations
- Cornell University (US)
- Rockefeller University (US)
- Venue
- Nature
- Published
- 1987-12
- Volume
- 330
- Issue
- 6149
- Pages
- 662-664
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2038434279
- Cited by
- 2,448
- References
- 1
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 19 · 2023: 17 · 2022: 13 · 2021: 24 · 2020: 24 · 2019: 32 · 2018: 31 · 2017: 24 · 2016: 40 · 2015: 33 · 2014: 44 · 2013: 43 · 2012: 46
- FWCI
- 95.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- TNF-α, septic shock, bacteremia, Escherichia coli, passive immunization, neutralizing monoclonal antibodies, F(ab')2 fragments, endotoxic shock, organ failure, renal failure, respiratory failure, stress hormones, baboons, sepsis treatment
- MeSH terms
- Animals, Antibodies, Monoclonal, Blood Pressure, Cardiac Output, Catecholamines, Glucagon, Immunization, Passive, Immunologic Techniques, Leukocyte Count, Papio, Shock, Septic, Tumor Necrosis Factor-alpha, Sepsis
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