Document Detail


Mechanism of IL-6-mediated cardiac dysfunction following trauma-hemorrhage.
MedLine Citation:
PMID:  16499925     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cardiac function is depressed and circulating IL-6 levels increase following trauma-hemorrhage (T-H). Although sustained elevated IL-6 after T-H correlate with poor outcome, the mechanism by which IL-6 produces cardiac dysfunction remains unknown. We hypothesized that IL-6-mediated cardiac depression is due to upregulation of NF-small ka, CyrillicB, ICAM, CINC and neutrophil infiltration. Six groups of male adult rats (275-300 g) were used: sham/T-H + vehicle, sham/T-H + IgG, sham/T-H + anti-IL-6mAb. Following midline laparotomy, 60% of the circulating blood was withdrawn and after 90 min, crystalloid fluid resuscitation was provided. Either normal goat IgG or anti-rat IL-6mAb (16.7 microg/kg BW) was administered intraperitoneally at 30 min after the onset of resuscitation. Two hours after resuscitation, cardiac function was measured, blood samples collected, cardiomyocytes isolated and intracellular IL-6 levels measured by flow cytometry. Cardiac IL-6, IL-6R, gp130, NF-small ka, CyrillicB, Ismall ka, CyrillicB-alpha, and ICAM-1 protein levels were measured in freshly isolated hearts by immunoblotting. Moreover, cardiac MPO activity and CINC-1 and -3 were measured. Cardiac function was depressed and cardiac IL-6, NF-small ka, CyrillicB, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after T-H. Administration of anti-IL-6mAb following T-H: 1) improved cardiac output (P<0.05); 2) downregulated cardiac IL-6 levels (P<0.05); 3) attenuated cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity (P<0.05). Administration of IgG, however, did not significantly influence these parameters. Thus, IL-6-mediated upregulation of cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity likely contributes to altered cardiac function following T-H and neutralization of IL-6 therefore appears to be an effective and novel adjunct for improving organ/cell function under those conditions.
Authors:
Shaolong Yang; Shunhua Hu; Ya-Ching Hsieh; Mashkoor A Choudhry; Loring W Rue; Kirby I Bland; Irshad H Chaudry
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-02-24
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  40     ISSN:  0022-2828     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-27     Completed Date:  2006-06-13     Revised Date:  2010-04-01    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  570-9     Citation Subset:  IM    
Affiliation:
Center for Surgical Research and Department of Surgery, The University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall, Room G094, Birmingham, AL 35294-0019, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / administration & dosage,  immunology
Gene Expression Regulation* / drug effects,  immunology
Interleukin-6 / blood*,  immunology
Male
Myocardium / immunology,  metabolism*,  pathology
Neutrophil Infiltration* / drug effects,  immunology
Rats
Rats, Sprague-Dawley
Shock, Hemorrhagic / blood*,  immunology,  pathology
Wounds and Injuries / blood*,  immunology,  pathology
Grant Support
ID/Acronym/Agency:
R37 GM39519/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Interleukin-6
Comments/Corrections
Erratum In:
J Mol Cell Cardiol. 2010 Feb;48(2):428

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