Linked Life Data

17313958

Source:http://linkedlifedata.com/resource/pubmed/id/17313958

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-3-12
pubmed:abstractText
Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely contributes to altered cardiac function following trauma-hemorrhage. Since IL-6R blockade after trauma-hemorrhage down-regulates cardiac IL-6 and improves cardiac functions, blockade of IL-6R following trauma-hemorrhage appears to be a novel and effective adjunct for improving organ and cell function under those conditions.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-2828
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
620-30
pubmed:dateRevised
2010-4-1
pubmed:meshHeading
pubmed-meshheading:17313958-Animals, pubmed-meshheading:17313958-Antibodies, pubmed-meshheading:17313958-Chemokine CXCL1, pubmed-meshheading:17313958-Chemokines, CXC, pubmed-meshheading:17313958-Disease Models, Animal, pubmed-meshheading:17313958-Down-Regulation, pubmed-meshheading:17313958-Heart, pubmed-meshheading:17313958-Hemorrhage, pubmed-meshheading:17313958-I-kappa B Kinase, pubmed-meshheading:17313958-Intercellular Adhesion Molecule-1, pubmed-meshheading:17313958-Interleukin-6, pubmed-meshheading:17313958-Male, pubmed-meshheading:17313958-NF-kappa B, pubmed-meshheading:17313958-Peroxidase, pubmed-meshheading:17313958-Rats, pubmed-meshheading:17313958-Rats, Sprague-Dawley, pubmed-meshheading:17313958-Receptors, Interleukin-6, pubmed-meshheading:17313958-Regional Blood Flow, pubmed-meshheading:17313958-Shock, pubmed-meshheading:17313958-Time Factors
pubmed:year
2007
pubmed:articleTitle
Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.
pubmed:affiliation
Center for Surgical Research and Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL 35294-0019, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural