Document Detail


Lung-derived macrophage migration inhibitory factor in sepsis induces cardio-circulatory depression.
MedLine Citation:
PMID:  17381395     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Acute lung injury is common during sepsis. Whereas gaseous exchange often can be supported adequately, death results frequently from cardio-circulatory depression, the mechanisms of which remain unclear. The aim of this study was to determine whether cardio-circulatory dysfunction during sepsis results from release of macrophage migration inhibitory factor (MIF) by the lung.
METHODS: Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in adult Sprague-Dawley rats. Macrophage MIF was measured in the plasma sampled from the right ventricle (pre-lung) and left atrium (post-lung).
RESULTS: The concentration of macrophage MIF in each of the post-lung samples was higher than in the corresponding pre-lung sample at 6 h (p = 0.015; paired t-test), 20 h (p = 0.008), and 30 h (p = 0.026) after the induction of sepsis. Next, rats that underwent CLP were treated with either saline (control) or our specific MIF inhibitor, (S, R )-3-(4-hydroxyphenyl)-4,5-dehydro-5-isoxazole acetic acid methyl ester (ISO-1). Echocardiography revealed that ISO-1 significantly improved the left ventricular end-diastolic volume index (p = 0.02), stroke volume index (p = 0.01), and cardiac index (p = 0.02) at 30 h after the induction of sepsis.
CONCLUSIONS: The lung appears to release significant amounts of macrophage MIF into the systemic circulation during late sepsis. Inhibition of MIF in a clinically relevant time frame blocked polymicrobial peritonitis-induced cardio-circulatory dysfunction. Inhibition of MIF may be a useful strategy to prevent cardio-circulatory deterioration associated with late sepsis.
Authors:
Tohru Sakuragi; Xinchun Lin; Christine N Metz; Kaie Ojamaa; Nina Kohn; Yousef Al-Abed; Edmund J Miller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Surgical infections     Volume:  8     ISSN:  1096-2964     ISO Abbreviation:  Surg Infect (Larchmt)     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-03-26     Completed Date:  2007-10-05     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  9815642     Medline TA:  Surg Infect (Larchmt)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29-40     Citation Subset:  IM    
Affiliation:
Department of Surgery, The Feinstein Institute for Medical Research, 360 Community Drive, Manhasset, NY 11030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiac Volume
Disease Models, Animal
Echocardiography
Immunologic Factors / pharmacology
Isoxazoles / pharmacology
Lung / immunology*
Macrophage Migration-Inhibitory Factors / antagonists & inhibitors,  biosynthesis*,  blood
Rats
Rats, Sprague-Dawley
Respiratory Distress Syndrome, Adult / complications*,  immunology
Sepsis / complications*,  immunology*
Shock / etiology*
Stroke Volume
Grant Support
ID/Acronym/Agency:
HL 081655/HL/NHLBI NIH HHS; R01 GM 60197/GM/NIGMS NIH HHS; R01 HL081655-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; 0/Immunologic Factors; 0/Isoxazoles; 0/Macrophage Migration-Inhibitory Factors
Comments/Corrections

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