Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

Monte S. Willis, Deborah L. Carlson, J. Michael DiMaio, Michael D. White, D. Jean White, Glenn A. Adams IV, Jureta W. Horton, Brett P. Giroir

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 ± 1.8%, compared with the normal controls (56.0 ± 2.6%). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number2 57-2
DOIs
StatePublished - Feb 2005

Fingerprint

Macrophage Migration-Inhibitory Factors
Wounds and Injuries
Endotoxins
Body Surface Area
Anti-Arrhythmia Agents
Neutralizing Antibodies
Monoclonal Antibodies
Antibodies
Serum
Proteins

Keywords

  • Cytokine
  • Endotoxin
  • Innate immunity
  • Lipopolysaccharide
  • Sepsis

ASJC Scopus subject areas

  • Physiology

Cite this

Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury. / Willis, Monte S.; Carlson, Deborah L.; DiMaio, J. Michael; White, Michael D.; White, D. Jean; Adams IV, Glenn A.; Horton, Jureta W.; Giroir, Brett P.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 2 57-2, 02.2005.

Research output: Contribution to journalArticle

Willis, Monte S. ; Carlson, Deborah L. ; DiMaio, J. Michael ; White, Michael D. ; White, D. Jean ; Adams IV, Glenn A. ; Horton, Jureta W. ; Giroir, Brett P. / Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 288, No. 2 57-2.
@article{9595c97dab8e4c2f91ba4fe03a5878c6,
title = "Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury",
abstract = "We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40{\%} total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 ± 1.8{\%}, compared with the normal controls (56.0 ± 2.6{\%}). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.",
keywords = "Cytokine, Endotoxin, Innate immunity, Lipopolysaccharide, Sepsis",
author = "Willis, {Monte S.} and Carlson, {Deborah L.} and DiMaio, {J. Michael} and White, {Michael D.} and White, {D. Jean} and {Adams IV}, {Glenn A.} and Horton, {Jureta W.} and Giroir, {Brett P.}",
year = "2005",
month = "2",
doi = "10.1152/ajpheart.00189.2004",
language = "English (US)",
volume = "288",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "2 57-2",

}

TY - JOUR

T1 - Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

AU - Willis, Monte S.

AU - Carlson, Deborah L.

AU - DiMaio, J. Michael

AU - White, Michael D.

AU - White, D. Jean

AU - Adams IV, Glenn A.

AU - Horton, Jureta W.

AU - Giroir, Brett P.

PY - 2005/2

Y1 - 2005/2

N2 - We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 ± 1.8%, compared with the normal controls (56.0 ± 2.6%). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.

AB - We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 ± 1.8%, compared with the normal controls (56.0 ± 2.6%). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.

KW - Cytokine

KW - Endotoxin

KW - Innate immunity

KW - Lipopolysaccharide

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=12344335328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12344335328&partnerID=8YFLogxK

U2 - 10.1152/ajpheart.00189.2004

DO - 10.1152/ajpheart.00189.2004

M3 - Article

C2 - 15388499

AN - SCOPUS:12344335328

VL - 288

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 2 57-2

ER -