Protection from septic shock by neutralization of macrophage migration inhibitory factor

Details

Serval ID
serval:BIB_212D4750B3FF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Protection from septic shock by neutralization of macrophage migration inhibitory factor
Journal
Nature Medicine
Author(s)
Calandra  T., Echtenacher  B., Roy  D. L., Pugin  J., Metz  C. N., Hultner  L., Heumann  D., Mannel  D., Bucala  R., Glauser  M. P.
ISSN
1078-8956 (Print)
Publication state
Published
Issued date
02/2000
Volume
6
Number
2
Pages
164-70
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Feb
Abstract
Identification of new therapeutic targets for the management of septic shock remains imperative as all investigational therapies, including anti-tumor necrosis factor (TNF) and anti-interleukin (IL)-1 agents, have uniformly failed to lower the mortality of critically ill patients with severe sepsis. We report here that macrophage migration inhibitory factor (MIF) is a critical mediator of septic shock. High concentrations of MIF were detected in the peritoneal exudate fluid and in the systemic circulation of mice with bacterial peritonitis. Experiments performed in TNFalpha knockout mice allowed a direct evaluation of the part played by MIF in sepsis in the absence of this pivotal cytokine of inflammation. Anti-MIF antibody protected TNFalpha knockout from lethal peritonitis induced by cecal ligation and puncture (CLP), providing evidence of an intrinsic contribution of MIF to the pathogenesis of sepsis. Anti-MIF antibody also protected normal mice from lethal peritonitis induced by both CLP and Escherichia coli, even when treatment was started up to 8 hours after CLP. Conversely, co-injection of recombinant MIF and E. coli markedly increased the lethality of peritonitis. Finally, high concentrations of MIF were detected in the plasma of patients with severe sepsis or septic shock. These studies define a critical part for MIF in the pathogenesis of septic shock and identify a new target for therapeutic intervention.
Keywords
Adolescent Adult Aged Aged, 80 and over Animals Bacterial Infections/metabolism/*prevention & control Female Humans Macrophage Migration-Inhibitory Factors/*antagonists & inhibitors/immunology/metabolism Male Mice Middle Aged Peritonitis/metabolism/prevention & control Shock, Septic/metabolism/*prevention & control
Pubmed
Web of science
Create date
25/01/2008 13:28
Last modification date
20/08/2019 12:57
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