Cited by 2,448Sepsis Diagnosis and TreatmentInflammation biomarkers and pathwaysImmune Response and Inflammation

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Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

Tracey, Kevin J., Fong, Yuman, Hesse, David G., Manogue, Kirk R., Lee, Annette T., Kuo, George C., Lowry, Stephen F., Cerami, Anthony·1987·Nature

DOI 10.1038/330662a0

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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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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)
ORCID: Tracey, Kevin J.
Fong, Yuman
Kuo, George C.
Cerami, Anthony
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1987-12
Volume: 330
Issue: 6149
Pages: 662-664
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/330662a0
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 › Critical Care and Intensive Care Medicine › 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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Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia

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