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Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
[Role of macrophage migration inhibitory factor in mice with sepsis and after effect of its intervention]
Zhen-hui Zhang1, Xiao-hui Chen, Pei-yi Lin
1Intensive Care Unit, the Second Affiliated Hospital of Guangzhou Medical College, Guangzhou 510260, Guangdong, China.
Objective:
To investigate the expression profile of macrophage migration inhibitory factor (MIF) in serum and lung tissues of mice with sepsis, and to explore the effect of MIF antagonist ISO-1 on sepsis in a murine sepsis model.
Methods:
Sepsis was reproduced in 40 mice by cecal ligation and puncture (CLP). Heart blood was obtained from 8 mice each at 12, 24, 36, 48 hours after CLP. The content of MIF in serum was determined by enzyme linked immunosorbent assay (ELISA). MIF mRNA and protein expressions in lung tissues of septic mice were assessed by reverse transcription-polymerase chain reaction (RT-PCR) or Western blotting. Another group of 40 mice were selected to investigate the role and the impact of MIF antagonist ISO-1 in septic mice.
Results:
The content of MIF in serum was higher in septic mice than that in sham operation group, and it peaked at 36 hours, and decreased at 48 hours, but still higher than that in sham operation group (all P<0.01). The MIF mRNA and protein expression in lung tissues of septic mice were higher than those in sham operation group, beginning at 12 hours, and peaked at 48 hours (P<0.05 or P<0.01). ISO-1, which was the antagonist of MIF, could elevate the surviving rate of animals with sepsis [60% (12/20) vs. 25% (5/20), P<0.05].
Conclusion:
MIF plays a role as a late mediator in sepsis, with a high expression of MIF in serum and lung tissue. ISO-1 can elevate the surviving rate in murine model of sepsis. It is concluded that MIF could be taken as a potential target of treatment of sepsis.
Insights
Macrophage migration inhibitory factor (MIF) is elevated in sepsis and acts as a late mediator. The MIF antagonist ISO-1 improved survival rates in a mouse sepsis model, suggesting MIF as a potential therapeutic target.
Area of Science:
- Immunology
- Pathophysiology
- Pharmacology
Context:
- Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in various disease states.
- Understanding the role of MIF in sepsis pathogenesis is crucial for developing novel therapeutic strategies.
Purpose:
- To investigate the expression profile of macrophage migration inhibitory factor (MIF) in serum and lung tissues of mice with sepsis.
- To explore the therapeutic effect of the MIF antagonist ISO-1 on sepsis in a murine model.
Summary:
- Sepsis was induced in mice via cecal ligation and puncture (CLP).
- Serum and lung tissue levels of MIF were significantly elevated in septic mice compared to controls, with peak expression observed at later time points.
- Administration of ISO-1, an MIF antagonist, significantly improved survival rates in septic mice.
Impact:
- MIF functions as a late-phase mediator in sepsis.
- Targeting MIF with antagonists like ISO-1 demonstrates therapeutic potential for sepsis.
- These findings highlight MIF as a promising target for sepsis treatment.