| Lung-derived macrophage migration inhibitory factor in sepsis induces cardio-circulatory depression. | |
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MedLine Citation:
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PMID: 17381395 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Tohru Sakuragi; Xinchun Lin; Christine N Metz; Kaie Ojamaa; Nina Kohn; Yousef Al-Abed; Edmund J Miller |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Surgical infections Volume: 8 ISSN: 1096-2964 ISO Abbreviation: Surg Infect (Larchmt) Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-03-26 Completed Date: 2007-10-05 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 9815642 Medline TA: Surg Infect (Larchmt) Country: United States |
Other Details:
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Languages: eng Pagination: 29-40 Citation Subset: IM |
Affiliation:
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Department of Surgery, The Feinstein Institute for Medical Research, 360 Community Drive, Manhasset, NY 11030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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HL 081655/HL/NHLBI NIH HHS; R01 GM 60197/GM/NIGMS NIH HHS; R01 HL081655-04/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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