Shock and tissue injury induced by recombinant human cachectin

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

Research output: Contribution to journalArticle

1989 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)470-474
Number of pages5
JournalScience
Volume234
Issue number4775
StatePublished - 1986

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Endotoxins
Shock
Tumor Necrosis Factor-alpha
Wounds and Injuries
Hyperkalemia
Acidosis
Hyperglycemia
Hypotension
Gastrointestinal Tract
Pneumonia
Proteins
Necrosis
Macrophages
Hemorrhage
Kidney

ASJC Scopus subject areas

  • General

Cite this

Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., ... Cerami, A. (1986). Shock and tissue injury induced by recombinant human cachectin. Science, 234(4775), 470-474.

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.

In: Science, Vol. 234, No. 4775, 1986, p. 470-474.

Research output: Contribution to journalArticle

Tracey, KJ, Beutler, B, Lowry, SF, Merryweather, J, Wolpe, S, Milsark, IW, Hariri, RJ, Fahey, TJ, Zentella, A, Albert, JD, Shires, GT & Cerami, A 1986, 'Shock and tissue injury induced by recombinant human cachectin', Science, vol. 234, no. 4775, pp. 470-474.
Tracey KJ, Beutler B, Lowry SF, Merryweather J, Wolpe S, Milsark IW et al. Shock and tissue injury induced by recombinant human cachectin. Science. 1986;234(4775):470-474.
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. / Shock and tissue injury induced by recombinant human cachectin. In: Science. 1986 ; Vol. 234, No. 4775. pp. 470-474.
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AU - Hariri, Robert J.

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AU - Cerami, Anthony

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