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

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. +4 more·1986·Science

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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Crossref · 10.1126/science.3764421

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45 of 45 references verified0 citation errors · 0 not checkable

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  • 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.”
  • Administration of TNF to healthy mammals, including humans, reproduces the hemodynamic, metabolic, immunological, and pathological manifestations of septic shock.

    “Administration of TNF to healthy mammals (including humans) reproduces the hemodynamic, metabolic, immunological, and pathological manifestations of the disease (4)”
  • TNF has the capacity to cause fever and localized inflammation.

    “Other pathophysiological activities ascribed to TNF were the capacity to cause fever and localized inflammation (4, 6).”

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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.
Venue
Science
Published
1986-10-24
Volume
234
Issue
4775
Pages
470-474
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
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 › Epidemiology › 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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