| Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock. | |
| | |
MedLine Citation:
|
PMID: 14738793 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Myocardial failure has a central role in the complex pathophysiology of septic shock and contributes to organ failure and death. During the sepsis-induced inflammatory process, specific factors are released that depress myocardial contractile function. We aimed to identify these mediators of myocardial depression in meningococcal septic shock. METHODS: We combined gene-expression profiling with protein and cellular methods to identify a serum factor causing cardiac dysfunction in meningococcal septic shock. We identified genes that were significantly upregulated in blood after exposure to meningococci. We then selected for further analysis those genes whose protein products had properties of a myocardial depressant factor--specifically a 12-25 kDa heat-stable protein that is released into serum shortly after onset of meningococcal infection. FINDINGS: We identified 174 significantly upregulated genes in meningococcus-infected blood: six encoded proteins that were of the predicted size and had characteristics of a myocardial depressant factor. Of these, interleukin 6 caused significant myocardial depression in vitro. Removal of interleukin 6 from serum samples of patients with meningococcaemia and from supernatants of inflammatory cells stimulated by meningococci in vitro abolished the negative inotropic activity. Furthermore, concentrations in serum of interleukin 6 strongly predicted degree of myocardial dysfunction and severity of disease in children with meningococcal septic shock. INTERPRETATION: Interleukin 6 is a mediator of myocardial depression in meningococcal disease. This cytokine and its downstream mediators could be a target for future treatment strategies. |
| | |
Authors:
|
Nazima Pathan; Cheryl A Hemingway; Ash A Alizadeh; Alick C Stephens; Jennifer C Boldrick; Emmanuelle E Oragui; Colm McCabe; Steven B Welch; Adeline Whitney; Peter O'Gara; Simon Nadel; David A Relman; Sian E Harding; Michael Levin |
Related Documents
:
|
2478983 - Metabolic changes and mitochondrial dysfunction early following transthoracic countersh... 18954703 - Management of sepsis: early resuscitation. 812613 - Regional myocardial function in the conscious dog during acute coronary occlusion and r... |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Lancet Volume: 363 ISSN: 1474-547X ISO Abbreviation: Lancet Publication Date: 2004 Jan |
Date Detail:
|
Created Date: 2004-01-23 Completed Date: 2004-03-05 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 2985213R Medline TA: Lancet Country: England |
Other Details:
|
Languages: eng Pagination: 203-9 Citation Subset: AIM; IM |
Affiliation:
|
Department of Paediatrics, Imperial College of Science, Technology and Medicine, W2 1PG, London, UK. n.pathan@imperial.ac.uk |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adult Animals Cardiac Output, Low / blood, physiopathology Cardiomyopathies / blood, physiopathology* Cytokines / blood, physiology Humans Interleukin-6 / blood, physiology* Male Meningococcal Infections / blood, physiopathology* Myocardial Contraction / physiology Myocardial Depressant Factor / blood, physiology Oligonucleotide Array Sequence Analysis Rats Rats, Sprague-Dawley Shock, Septic / blood, physiopathology* |
| Chemical | |
Reg. No./Substance:
|
0/Cytokines; 0/Interleukin-6; 0/Myocardial Depressant Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcane...
Next Document: Total energy expenditure and physical activity in young Scottish children: mixed longitudinal study.