Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock
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 myocard...
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| Veröffentlicht in: | The Lancet (British edition) 2004-01, Vol.363 (9404), p.203-209 |
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| creator | Pathan, Nazima Hemingway, Cheryl A Alizadeh, Ash A Stephens, Alick C Boldrick, Jennifer C Oragui, Emmanuelle E McCabe, Colm Welch, Steven B Whitney, Adeline O'Gara, Peter Nadel, Simon Relman, David A Harding, Sian E Levin, Michael |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1016/S0140-6736(03)15326-3 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/S0140-6736(03)15326-3</identifier><identifier>PMID: 14738793</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>Adult ; Animals ; Biological and medical sciences ; Cardiac Output, Low - blood ; Cardiac Output, Low - physiopathology ; Cardiomyopathies - blood ; Cardiomyopathies - physiopathology ; Cardiovascular disease ; Cytokines - blood ; Cytokines - physiology ; General aspects ; Genes ; Humans ; In Vitro Techniques ; Interleukin-6 - blood ; Interleukin-6 - physiology ; Male ; Medical sciences ; Medical treatment ; Meningococcal Infections - blood ; Meningococcal Infections - physiopathology ; Myocardial Contraction - physiology ; Myocardial Depressant Factor - blood ; Myocardial Depressant Factor - physiology ; Oligonucleotide Array Sequence Analysis ; Rats ; Rats, Sprague-Dawley ; Shock, Septic - blood ; Shock, Septic - physiopathology</subject><ispartof>The Lancet (British edition), 2004-01, Vol.363 (9404), p.203-209</ispartof><rights>2004 Elsevier Ltd</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Lancet Ltd. Jan 17, 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c531t-1d83c14a75df6a9a0de64bae2c9894e60908b5fea822c70e9d27ce056bedac553</citedby><cites>FETCH-LOGICAL-c531t-1d83c14a75df6a9a0de64bae2c9894e60908b5fea822c70e9d27ce056bedac553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/199119895?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,782,786,3554,27933,27934,46004,64394,64396,64398,72478</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15793105$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14738793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pathan, Nazima</creatorcontrib><creatorcontrib>Hemingway, Cheryl A</creatorcontrib><creatorcontrib>Alizadeh, Ash A</creatorcontrib><creatorcontrib>Stephens, Alick C</creatorcontrib><creatorcontrib>Boldrick, Jennifer C</creatorcontrib><creatorcontrib>Oragui, Emmanuelle E</creatorcontrib><creatorcontrib>McCabe, Colm</creatorcontrib><creatorcontrib>Welch, Steven B</creatorcontrib><creatorcontrib>Whitney, Adeline</creatorcontrib><creatorcontrib>O'Gara, Peter</creatorcontrib><creatorcontrib>Nadel, Simon</creatorcontrib><creatorcontrib>Relman, David A</creatorcontrib><creatorcontrib>Harding, Sian E</creatorcontrib><creatorcontrib>Levin, Michael</creatorcontrib><title>Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>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.
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.
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.
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.</description><subject>Adult</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiac Output, Low - blood</subject><subject>Cardiac Output, Low - physiopathology</subject><subject>Cardiomyopathies - blood</subject><subject>Cardiomyopathies - physiopathology</subject><subject>Cardiovascular disease</subject><subject>Cytokines - blood</subject><subject>Cytokines - physiology</subject><subject>General aspects</subject><subject>Genes</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Interleukin-6 - blood</subject><subject>Interleukin-6 - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medical treatment</subject><subject>Meningococcal Infections - blood</subject><subject>Meningococcal Infections - physiopathology</subject><subject>Myocardial Contraction - 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B</au><au>Whitney, Adeline</au><au>O'Gara, Peter</au><au>Nadel, Simon</au><au>Relman, David A</au><au>Harding, Sian E</au><au>Levin, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>2004-01-17</date><risdate>2004</risdate><volume>363</volume><issue>9404</issue><spage>203</spage><epage>209</epage><pages>203-209</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>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.
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.
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.
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.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>14738793</pmid><doi>10.1016/S0140-6736(03)15326-3</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animals Biological and medical sciences Cardiac Output, Low - blood Cardiac Output, Low - physiopathology Cardiomyopathies - blood Cardiomyopathies - physiopathology Cardiovascular disease Cytokines - blood Cytokines - physiology General aspects Genes Humans In Vitro Techniques Interleukin-6 - blood Interleukin-6 - physiology Male Medical sciences Medical treatment Meningococcal Infections - blood Meningococcal Infections - physiopathology Myocardial Contraction - physiology Myocardial Depressant Factor - blood Myocardial Depressant Factor - physiology Oligonucleotide Array Sequence Analysis Rats Rats, Sprague-Dawley Shock, Septic - blood Shock, Septic - physiopathology |
| title | Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock |
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