Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog

K. J. Tracey, S. F. Lowry, T. J. Fahey, J. D. Albert, Y. Fong, D. Hesse, B. Beutler, K. R. Manogue, S. Calvano, H. Wei

Research output: Contribution to journalArticle

385 Citations (Scopus)

Abstract

Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.

Original languageEnglish (US)
Pages (from-to)415-422
Number of pages8
JournalSurgery Gynecology and Obstetrics
Volume164
Issue number5
StatePublished - 1987

Fingerprint

Shock
Tumor Necrosis Factor-alpha
Hormones
Dogs
Endotoxemia
Membrane Potentials
Kidney Papillary Necrosis
Necrosis
Intra Arterial Infusions
Hindlimb
Glucagon
Hypotension
Catecholamines
Hydrocortisone
Lactic Acid
Pneumonia
Skeletal Muscle
Thrombosis
Hemodynamics
Macrophages

ASJC Scopus subject areas

  • Surgery
  • Obstetrics and Gynecology

Cite this

Tracey, K. J., Lowry, S. F., Fahey, T. J., Albert, J. D., Fong, Y., Hesse, D., ... Wei, H. (1987). Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surgery Gynecology and Obstetrics, 164(5), 415-422.

Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. / Tracey, K. J.; Lowry, S. F.; Fahey, T. J.; Albert, J. D.; Fong, Y.; Hesse, D.; Beutler, B.; Manogue, K. R.; Calvano, S.; Wei, H.

In: Surgery Gynecology and Obstetrics, Vol. 164, No. 5, 1987, p. 415-422.

Research output: Contribution to journalArticle

Tracey, KJ, Lowry, SF, Fahey, TJ, Albert, JD, Fong, Y, Hesse, D, Beutler, B, Manogue, KR, Calvano, S & Wei, H 1987, 'Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog', Surgery Gynecology and Obstetrics, vol. 164, no. 5, pp. 415-422.
Tracey KJ, Lowry SF, Fahey TJ, Albert JD, Fong Y, Hesse D et al. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surgery Gynecology and Obstetrics. 1987;164(5):415-422.
Tracey, K. J. ; Lowry, S. F. ; Fahey, T. J. ; Albert, J. D. ; Fong, Y. ; Hesse, D. ; Beutler, B. ; Manogue, K. R. ; Calvano, S. ; Wei, H. / Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. In: Surgery Gynecology and Obstetrics. 1987 ; Vol. 164, No. 5. pp. 415-422.
@article{506e5965a4d647898d5515a1a24cca42,
title = "Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog",
abstract = "Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.",
author = "Tracey, {K. J.} and Lowry, {S. F.} and Fahey, {T. J.} and Albert, {J. D.} and Y. Fong and D. Hesse and B. Beutler and Manogue, {K. R.} and S. Calvano and H. Wei",
year = "1987",
language = "English (US)",
volume = "164",
pages = "415--422",
journal = "Journal of the American College of Surgeons",
issn = "1072-7515",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog

AU - Tracey, K. J.

AU - Lowry, S. F.

AU - Fahey, T. J.

AU - Albert, J. D.

AU - Fong, Y.

AU - Hesse, D.

AU - Beutler, B.

AU - Manogue, K. R.

AU - Calvano, S.

AU - Wei, H.

PY - 1987

Y1 - 1987

N2 - Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.

AB - Cachectin/tumor necrosis factor has been implicated as a mediator of lethal endotoxemia, but the metabolic and hemodynamic responses to this macrophage-derived peptide have been incompletely characterized. Cachectin was administered by intra-arterial infusion in two groups of beagle dogs at lethal (100 micrograms per kilogram) and sublethal (10 micrograms per kilogram) doses. The infusion produced serum cachectin levels (1 to 50 nanomoles per liter) similar to those achieved after experimental endotoxemia. The lethal response to cachectin was characterized by progressive hypotension, shock and death within three hours. Histopathologic findings included acute inflammation of the pulmonary interstitium, intravascular thrombosis with hemorrhagic necrosis, adrenal medullary necrosis and acute renal tubular necrosis. Cachectin infusion precipitated significant increases of plasma catecholamines, cortisol and glucagon in a dose response manner. Cachectin infused directly into the isolated hindlimb mediated reductions of skeletal muscle resting transmembrane potential and stimulated lactate efflux. Cachectin appears to occupy a crucial role in physiopathologic responses to infection, and likely participates in the mobilization of host energy stores, intravascular depletion and shock after lethal endotoxemia.

UR - http://www.scopus.com/inward/record.url?scp=0023183621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023183621&partnerID=8YFLogxK

M3 - Article

C2 - 3576418

AN - SCOPUS:0023183621

VL - 164

SP - 415

EP - 422

JO - Journal of the American College of Surgeons

JF - Journal of the American College of Surgeons

SN - 1072-7515

IS - 5

ER -