Immunologic alterations in a murine model of hemorrhagic shock

Ramon Zapata Sirvent, J. F. Hansbrough, M. C. Cox, W. H. Carter

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: To study multiple immune parameters in mice subjected to severe hemorrhage without fluid resuscitation. Study Design: Controlled animal study. Anesthetized, female mice were hemorrhaged by tail bleeding. Immune parameters (spleen T-cell proliferation and activation, intracellular calcium flux, cytokine production, peritoneal neutrophil respiratory burst, and survival after intraabdominal septic challenge) were measured at 24, 48, and 72 hrs after hemorrhage. Measurements and Main Results: T-cell proliferation was decreased in animals after two 20% blood volume hemorrhages, 30 mins apart; single 30%, 40%, and 50% blood volume hemorrhages did not depress proliferation. 'Helper/inducer' T cells from twice-hemorrhaged mice showed decreased expression of activation antigens (interleukin-2 receptor, Ia) after mitogen stimulation. In contrast, 'suppressor/cytotoxic' T cells displayed increased activation, shown by augmented expression of interleukin- 2 receptor and Ia antigens. Leukocyte production of prostaglandin E2, a mediator frequently implicated in immune down-regulation, was unaffected by hemorrhage. Secretion of tumor necrosis factor-α (TNF-α) in culture was increased when cells were harvested 48 hrs after injury. Intracellular calcium flux in stimulated lymphocytes was decreased 24 hrs after hemorrhage, suggesting deranged intracellular signal transduction. Respiratory burst activity of peritoneal neutrophils was unchanged following hemorrhage. When animals were subjected to septic challenge, the survival rate was markedly decreased after two hemorrhages (when sepsis was induced 24 hrs after hemorrhage). By 72 hrs posthemorrhage, most of the immunologic alterations, including resistance to septic challenge, had resolved. Conclusions: This uninstrumented hemorrhagic shock model allows quantification of multiple immune derangements. Immune suppression was identified after two smaller (20% blood volume) hemorrhages, but not after a single, larger hemorrhage. Immune derangements are maximal at 24 hrs posthemorrhage, and resolve in the subsequent 48 hrs.

Original languageEnglish (US)
Pages (from-to)508-517
Number of pages10
JournalCritical Care Medicine
Volume20
Issue number4
DOIs
StatePublished - Jan 1 1992
Externally publishedYes

Fingerprint

Hemorrhagic Shock
Hemorrhage
Blood Volume
Respiratory Burst
Interleukin-2 Receptors
T-Lymphocytes
Neutrophils
Cell Proliferation
Calcium
Histocompatibility Antigens Class II
Helper-Inducer T-Lymphocytes
Mitogens
Dinoprostone
Resuscitation
Tail
Signal Transduction
Sepsis
Leukocytes
Down-Regulation
Spleen

Keywords

  • calcium
  • cytokines
  • hemorrhage
  • immune function
  • neutrophil
  • prostaglandins
  • sepsis
  • shock
  • T- cell
  • tumor necrosis factor

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Immunologic alterations in a murine model of hemorrhagic shock. / Zapata Sirvent, Ramon; Hansbrough, J. F.; Cox, M. C.; Carter, W. H.

In: Critical Care Medicine, Vol. 20, No. 4, 01.01.1992, p. 508-517.

Research output: Contribution to journalArticle

Zapata Sirvent, Ramon ; Hansbrough, J. F. ; Cox, M. C. ; Carter, W. H. / Immunologic alterations in a murine model of hemorrhagic shock. In: Critical Care Medicine. 1992 ; Vol. 20, No. 4. pp. 508-517.
@article{8a26225efeab459c92444e790f909d33,
title = "Immunologic alterations in a murine model of hemorrhagic shock",
abstract = "Objective: To study multiple immune parameters in mice subjected to severe hemorrhage without fluid resuscitation. Study Design: Controlled animal study. Anesthetized, female mice were hemorrhaged by tail bleeding. Immune parameters (spleen T-cell proliferation and activation, intracellular calcium flux, cytokine production, peritoneal neutrophil respiratory burst, and survival after intraabdominal septic challenge) were measured at 24, 48, and 72 hrs after hemorrhage. Measurements and Main Results: T-cell proliferation was decreased in animals after two 20{\%} blood volume hemorrhages, 30 mins apart; single 30{\%}, 40{\%}, and 50{\%} blood volume hemorrhages did not depress proliferation. 'Helper/inducer' T cells from twice-hemorrhaged mice showed decreased expression of activation antigens (interleukin-2 receptor, Ia) after mitogen stimulation. In contrast, 'suppressor/cytotoxic' T cells displayed increased activation, shown by augmented expression of interleukin- 2 receptor and Ia antigens. Leukocyte production of prostaglandin E2, a mediator frequently implicated in immune down-regulation, was unaffected by hemorrhage. Secretion of tumor necrosis factor-α (TNF-α) in culture was increased when cells were harvested 48 hrs after injury. Intracellular calcium flux in stimulated lymphocytes was decreased 24 hrs after hemorrhage, suggesting deranged intracellular signal transduction. Respiratory burst activity of peritoneal neutrophils was unchanged following hemorrhage. When animals were subjected to septic challenge, the survival rate was markedly decreased after two hemorrhages (when sepsis was induced 24 hrs after hemorrhage). By 72 hrs posthemorrhage, most of the immunologic alterations, including resistance to septic challenge, had resolved. Conclusions: This uninstrumented hemorrhagic shock model allows quantification of multiple immune derangements. Immune suppression was identified after two smaller (20{\%} blood volume) hemorrhages, but not after a single, larger hemorrhage. Immune derangements are maximal at 24 hrs posthemorrhage, and resolve in the subsequent 48 hrs.",
keywords = "calcium, cytokines, hemorrhage, immune function, neutrophil, prostaglandins, sepsis, shock, T- cell, tumor necrosis factor",
author = "{Zapata Sirvent}, Ramon and Hansbrough, {J. F.} and Cox, {M. C.} and Carter, {W. H.}",
year = "1992",
month = "1",
day = "1",
doi = "10.1097/00003246-199204000-00013",
language = "English (US)",
volume = "20",
pages = "508--517",
journal = "Critical Care Medicine",
issn = "0090-3493",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Immunologic alterations in a murine model of hemorrhagic shock

AU - Zapata Sirvent, Ramon

AU - Hansbrough, J. F.

AU - Cox, M. C.

AU - Carter, W. H.

PY - 1992/1/1

Y1 - 1992/1/1

N2 - Objective: To study multiple immune parameters in mice subjected to severe hemorrhage without fluid resuscitation. Study Design: Controlled animal study. Anesthetized, female mice were hemorrhaged by tail bleeding. Immune parameters (spleen T-cell proliferation and activation, intracellular calcium flux, cytokine production, peritoneal neutrophil respiratory burst, and survival after intraabdominal septic challenge) were measured at 24, 48, and 72 hrs after hemorrhage. Measurements and Main Results: T-cell proliferation was decreased in animals after two 20% blood volume hemorrhages, 30 mins apart; single 30%, 40%, and 50% blood volume hemorrhages did not depress proliferation. 'Helper/inducer' T cells from twice-hemorrhaged mice showed decreased expression of activation antigens (interleukin-2 receptor, Ia) after mitogen stimulation. In contrast, 'suppressor/cytotoxic' T cells displayed increased activation, shown by augmented expression of interleukin- 2 receptor and Ia antigens. Leukocyte production of prostaglandin E2, a mediator frequently implicated in immune down-regulation, was unaffected by hemorrhage. Secretion of tumor necrosis factor-α (TNF-α) in culture was increased when cells were harvested 48 hrs after injury. Intracellular calcium flux in stimulated lymphocytes was decreased 24 hrs after hemorrhage, suggesting deranged intracellular signal transduction. Respiratory burst activity of peritoneal neutrophils was unchanged following hemorrhage. When animals were subjected to septic challenge, the survival rate was markedly decreased after two hemorrhages (when sepsis was induced 24 hrs after hemorrhage). By 72 hrs posthemorrhage, most of the immunologic alterations, including resistance to septic challenge, had resolved. Conclusions: This uninstrumented hemorrhagic shock model allows quantification of multiple immune derangements. Immune suppression was identified after two smaller (20% blood volume) hemorrhages, but not after a single, larger hemorrhage. Immune derangements are maximal at 24 hrs posthemorrhage, and resolve in the subsequent 48 hrs.

AB - Objective: To study multiple immune parameters in mice subjected to severe hemorrhage without fluid resuscitation. Study Design: Controlled animal study. Anesthetized, female mice were hemorrhaged by tail bleeding. Immune parameters (spleen T-cell proliferation and activation, intracellular calcium flux, cytokine production, peritoneal neutrophil respiratory burst, and survival after intraabdominal septic challenge) were measured at 24, 48, and 72 hrs after hemorrhage. Measurements and Main Results: T-cell proliferation was decreased in animals after two 20% blood volume hemorrhages, 30 mins apart; single 30%, 40%, and 50% blood volume hemorrhages did not depress proliferation. 'Helper/inducer' T cells from twice-hemorrhaged mice showed decreased expression of activation antigens (interleukin-2 receptor, Ia) after mitogen stimulation. In contrast, 'suppressor/cytotoxic' T cells displayed increased activation, shown by augmented expression of interleukin- 2 receptor and Ia antigens. Leukocyte production of prostaglandin E2, a mediator frequently implicated in immune down-regulation, was unaffected by hemorrhage. Secretion of tumor necrosis factor-α (TNF-α) in culture was increased when cells were harvested 48 hrs after injury. Intracellular calcium flux in stimulated lymphocytes was decreased 24 hrs after hemorrhage, suggesting deranged intracellular signal transduction. Respiratory burst activity of peritoneal neutrophils was unchanged following hemorrhage. When animals were subjected to septic challenge, the survival rate was markedly decreased after two hemorrhages (when sepsis was induced 24 hrs after hemorrhage). By 72 hrs posthemorrhage, most of the immunologic alterations, including resistance to septic challenge, had resolved. Conclusions: This uninstrumented hemorrhagic shock model allows quantification of multiple immune derangements. Immune suppression was identified after two smaller (20% blood volume) hemorrhages, but not after a single, larger hemorrhage. Immune derangements are maximal at 24 hrs posthemorrhage, and resolve in the subsequent 48 hrs.

KW - calcium

KW - cytokines

KW - hemorrhage

KW - immune function

KW - neutrophil

KW - prostaglandins

KW - sepsis

KW - shock

KW - T- cell

KW - tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=0026683957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026683957&partnerID=8YFLogxK

U2 - 10.1097/00003246-199204000-00013

DO - 10.1097/00003246-199204000-00013

M3 - Article

C2 - 1559365

AN - SCOPUS:0026683957

VL - 20

SP - 508

EP - 517

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 4

ER -