Cited by 2,549Sepsis Diagnosis and TreatmentImmune Response and InflammationInflammation biomarkers and pathways

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Shock and Tissue Injury Induced by Recombinant Human Cachectin

Tracey, Kevin J., Beutler, Bruce, Lowry, Stephen F., Merryweather, James, Wolpe, Stephen, Milsark, Ian W., Hariri, Robert J., Fahey, Thomas J., Zentella, Alejandro, Albert, James D., Shires, G. Tom, Cerami, Anthony·1986·Science

DOI 10.1126/science.3764421

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Abstract

Cachectin (tumor necrosis factor), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. Recombinant human cachectin was infused into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin.

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Authors: Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., Shires, G. T., & Cerami, A.
Affiliations: Weill Cornell Medical Center (US)
Department of Surgery, New York Hospital-Cornell Medical Center, New York, NY 10021.
ORCID: Tracey, Kevin J.
Beutler, Bruce
Hariri, Robert J.
Fahey, Thomas J.
Cerami, Anthony
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1986-10-24
Volume: 234
Issue: 4775
Pages: 470-474
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.3764421
OpenAlex: W1968713831
Cited by: 2,549
References: 45
Citations by year: 2026: 8 · 2025: 11 · 2024: 16 · 2023: 12 · 2022: 13 · 2021: 18 · 2020: 19 · 2019: 18 · 2018: 21 · 2017: 21 · 2016: 28 · 2015: 19 · 2014: 30 · 2013: 38 · 2012: 29
FWCI: 107.88
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
Keywords: TNF-α, endotoxin, septic shock, tissue damage, hypotension, metabolic acidosis, hemoconcentration, respiratory arrest, hyperglycemia, hyperkalemia, pulmonary hemorrhage, acute tubular necrosis, gastrointestinal bleeding, macrophages
MeSH terms: Animals, Blood Glucose, Endotoxins, Female, Glycoproteins, Humans, Potassium, Recombinant Proteins, Shock, Sodium, Tumor Necrosis Factor-alpha, Rats

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Shock and Tissue Injury Induced by Recombinant Human Cachectin

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