Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma

Matthias Majetschak, Stephen M. Cohn, Udo Obertacke, Kenneth G Proctor, Ernest F J Block, Basil A. Pruitt

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: Recent studies suggest that extracellular ubiquitin could have a physiologic role in immunodepression in sepsis and trauma. The therapeutic potential of exogenous ubiquitin after trauma has not been examined. To fill this gap, we designed a series of experiments in a clinically relevant trauma model. Methods: Forty minutes after femur fractures and hemorrhage, swine received 1.3 mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor necrosis factor-α (TNFα) production ex vivo. TNFα and ubiquitin were quantified with enzyme-linked immunosorbent assay. Results: Intravenous ubiquitin had no significant hemodynamic effect in normal animals. After injury, ubiquitin significantly reduced fluid requirements by at least 60% (p < 0.05). The injury was associated with transient immunodepression, as reflected by reduced endotoxin-evoked TNFα production by 40% to 50%. With ubiquitin, this response remained depressed for 100 to 160 minutes (p < 0.05), but fully recovered to baseline with albumin. Conclusion: Ubiquitin is apparently safe and effective for reducing fluid requirements as a measure of diffuse capillary leak. This immunomodulatory property suggests a new therapeutic approach after injury in particular, and for infectious and noninfectious inflammation in general.

Original languageEnglish
Pages (from-to)991-1000
Number of pages10
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume56
Issue number5
StatePublished - May 1 2004

Fingerprint

Ubiquitin
Resuscitation
Wounds and Injuries
Tumor Necrosis Factor-alpha
Therapeutics
Endotoxins
Immunosuppression
Hemodynamics
Bovine Serum Albumin
Femur
Albumins
Sepsis
Leukocytes
Swine
Enzyme-Linked Immunosorbent Assay
Hemorrhage
Inflammation
Serum

Keywords

  • Capillary leak
  • Endotoxin
  • Fluid requirements
  • Immunomodulation
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Surgery

Cite this

Majetschak, M., Cohn, S. M., Obertacke, U., Proctor, K. G., Block, E. F. J., & Pruitt, B. A. (2004). Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma. Journal of Trauma - Injury, Infection and Critical Care, 56(5), 991-1000.

Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma. / Majetschak, Matthias; Cohn, Stephen M.; Obertacke, Udo; Proctor, Kenneth G; Block, Ernest F J; Pruitt, Basil A.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 56, No. 5, 01.05.2004, p. 991-1000.

Research output: Contribution to journalArticle

Majetschak, M, Cohn, SM, Obertacke, U, Proctor, KG, Block, EFJ & Pruitt, BA 2004, 'Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma', Journal of Trauma - Injury, Infection and Critical Care, vol. 56, no. 5, pp. 991-1000.
Majetschak, Matthias ; Cohn, Stephen M. ; Obertacke, Udo ; Proctor, Kenneth G ; Block, Ernest F J ; Pruitt, Basil A. / Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma. In: Journal of Trauma - Injury, Infection and Critical Care. 2004 ; Vol. 56, No. 5. pp. 991-1000.
@article{6534d5e0e42a4d919d43c04575ec9569,
title = "Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma",
abstract = "Background: Recent studies suggest that extracellular ubiquitin could have a physiologic role in immunodepression in sepsis and trauma. The therapeutic potential of exogenous ubiquitin after trauma has not been examined. To fill this gap, we designed a series of experiments in a clinically relevant trauma model. Methods: Forty minutes after femur fractures and hemorrhage, swine received 1.3 mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor necrosis factor-α (TNFα) production ex vivo. TNFα and ubiquitin were quantified with enzyme-linked immunosorbent assay. Results: Intravenous ubiquitin had no significant hemodynamic effect in normal animals. After injury, ubiquitin significantly reduced fluid requirements by at least 60{\%} (p < 0.05). The injury was associated with transient immunodepression, as reflected by reduced endotoxin-evoked TNFα production by 40{\%} to 50{\%}. With ubiquitin, this response remained depressed for 100 to 160 minutes (p < 0.05), but fully recovered to baseline with albumin. Conclusion: Ubiquitin is apparently safe and effective for reducing fluid requirements as a measure of diffuse capillary leak. This immunomodulatory property suggests a new therapeutic approach after injury in particular, and for infectious and noninfectious inflammation in general.",
keywords = "Capillary leak, Endotoxin, Fluid requirements, Immunomodulation, Tumor necrosis factor-α",
author = "Matthias Majetschak and Cohn, {Stephen M.} and Udo Obertacke and Proctor, {Kenneth G} and Block, {Ernest F J} and Pruitt, {Basil A.}",
year = "2004",
month = "5",
day = "1",
language = "English",
volume = "56",
pages = "991--1000",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Therapeutic potential of exogenous ubiquitin during resuscitation from severe trauma

AU - Majetschak, Matthias

AU - Cohn, Stephen M.

AU - Obertacke, Udo

AU - Proctor, Kenneth G

AU - Block, Ernest F J

AU - Pruitt, Basil A.

PY - 2004/5/1

Y1 - 2004/5/1

N2 - Background: Recent studies suggest that extracellular ubiquitin could have a physiologic role in immunodepression in sepsis and trauma. The therapeutic potential of exogenous ubiquitin after trauma has not been examined. To fill this gap, we designed a series of experiments in a clinically relevant trauma model. Methods: Forty minutes after femur fractures and hemorrhage, swine received 1.3 mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor necrosis factor-α (TNFα) production ex vivo. TNFα and ubiquitin were quantified with enzyme-linked immunosorbent assay. Results: Intravenous ubiquitin had no significant hemodynamic effect in normal animals. After injury, ubiquitin significantly reduced fluid requirements by at least 60% (p < 0.05). The injury was associated with transient immunodepression, as reflected by reduced endotoxin-evoked TNFα production by 40% to 50%. With ubiquitin, this response remained depressed for 100 to 160 minutes (p < 0.05), but fully recovered to baseline with albumin. Conclusion: Ubiquitin is apparently safe and effective for reducing fluid requirements as a measure of diffuse capillary leak. This immunomodulatory property suggests a new therapeutic approach after injury in particular, and for infectious and noninfectious inflammation in general.

AB - Background: Recent studies suggest that extracellular ubiquitin could have a physiologic role in immunodepression in sepsis and trauma. The therapeutic potential of exogenous ubiquitin after trauma has not been examined. To fill this gap, we designed a series of experiments in a clinically relevant trauma model. Methods: Forty minutes after femur fractures and hemorrhage, swine received 1.3 mg of ubiquitin per kilogram or bovine serum albumin intravenously followed by fluid resuscitation to maintain systemic hemodynamics. Leukocyte function and the immunomodulatory capacity of serum were assessed measuring endotoxin-evoked tumor necrosis factor-α (TNFα) production ex vivo. TNFα and ubiquitin were quantified with enzyme-linked immunosorbent assay. Results: Intravenous ubiquitin had no significant hemodynamic effect in normal animals. After injury, ubiquitin significantly reduced fluid requirements by at least 60% (p < 0.05). The injury was associated with transient immunodepression, as reflected by reduced endotoxin-evoked TNFα production by 40% to 50%. With ubiquitin, this response remained depressed for 100 to 160 minutes (p < 0.05), but fully recovered to baseline with albumin. Conclusion: Ubiquitin is apparently safe and effective for reducing fluid requirements as a measure of diffuse capillary leak. This immunomodulatory property suggests a new therapeutic approach after injury in particular, and for infectious and noninfectious inflammation in general.

KW - Capillary leak

KW - Endotoxin

KW - Fluid requirements

KW - Immunomodulation

KW - Tumor necrosis factor-α

UR - http://www.scopus.com/inward/record.url?scp=2942739032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942739032&partnerID=8YFLogxK

M3 - Article

C2 - 15179237

AN - SCOPUS:2942739032

VL - 56

SP - 991

EP - 1000

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 5

ER -