Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis
Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K ATP -channel blocker and broad-spe...
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| Veröffentlicht in: | Clinical infectious diseases 2011-03, Vol.52 (6), p.717-725 |
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| creator | Koh, Gavin C. K. W. Maude, Rapeephan R. Schreiber, M. Fernanda Limmathurotsakul, Direk Wiersinga, W. Joost Wuthiekanun, Vanaporn Lee, Sue J. Mahavanakul, Weera Chaowagul, Wipada Chierakul, Wirongrong White, Nicholas J. van der Poll, Tom Day, Nicholas P. J. Dougan, Gordon Peacock, Sharon J. |
| description | Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K ATP -channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, incljuding inhibition of inflammasome assembly and would be predicted to influence the host response to infection. Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system. |
| doi_str_mv | 10.1093/cid/ciq192 |
| format | Article |
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K. W. ; Maude, Rapeephan R. ; Schreiber, M. Fernanda ; Limmathurotsakul, Direk ; Wiersinga, W. Joost ; Wuthiekanun, Vanaporn ; Lee, Sue J. ; Mahavanakul, Weera ; Chaowagul, Wipada ; Chierakul, Wirongrong ; White, Nicholas J. ; van der Poll, Tom ; Day, Nicholas P. J. ; Dougan, Gordon ; Peacock, Sharon J.</creator><creatorcontrib>Koh, Gavin C. K. W. ; Maude, Rapeephan R. ; Schreiber, M. Fernanda ; Limmathurotsakul, Direk ; Wiersinga, W. Joost ; Wuthiekanun, Vanaporn ; Lee, Sue J. ; Mahavanakul, Weera ; Chaowagul, Wipada ; Chierakul, Wirongrong ; White, Nicholas J. ; van der Poll, Tom ; Day, Nicholas P. J. ; Dougan, Gordon ; Peacock, Sharon J.</creatorcontrib><description>Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K ATP -channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, incljuding inhibition of inflammasome assembly and would be predicted to influence the host response to infection. Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciq192</identifier><identifier>PMID: 21293047</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>ABC transporters ; Adult ; and Commentaries ; Anti-Inflammatory Agents - administration & dosage ; Antiinflammatories ; ARTICLES AND COMMENTARIES ; Bacterial diseases ; Biological and medical sciences ; Burkholderia pseudomallei - isolation & purification ; Cohort Studies ; Correlation analysis ; Diabetes ; Diabetes complications ; Female ; Gene expression ; Glyburide - administration & dosage ; Gram-negative bacteria ; Hospital admissions ; Human bacterial diseases ; Humans ; Immune system ; Infections ; Infectious diseases ; Leukocytes ; Male ; Medical sciences ; Melioidosis ; Melioidosis - drug therapy ; Melioidosis - mortality ; Middle Aged ; Mortality ; Neutrophils ; Prospective Studies ; Sepsis ; Sepsis - drug therapy ; Sepsis - microbiology ; Sepsis - mortality ; Survival Analysis ; Treatment Outcome ; Tropical bacterial diseases ; Type 2 diabetes mellitus</subject><ispartof>Clinical infectious diseases, 2011-03, Vol.52 (6), p.717-725</ispartof><rights>Copyright © 2011 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail:journals.permissions@oup.com. 2011</rights><rights>2015 INIST-CNRS</rights><rights>Copyright University of Chicago, acting through its Press Mar 15, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-b2a5f61cf4aa2b31d36bff069f9f329e505d999d7fc7e479b4f090624072a7f13</citedby><cites>FETCH-LOGICAL-c519t-b2a5f61cf4aa2b31d36bff069f9f329e505d999d7fc7e479b4f090624072a7f13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/29777382$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/29777382$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,1584,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24096357$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21293047$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Koh, Gavin C. K. W.</creatorcontrib><creatorcontrib>Maude, Rapeephan R.</creatorcontrib><creatorcontrib>Schreiber, M. Fernanda</creatorcontrib><creatorcontrib>Limmathurotsakul, Direk</creatorcontrib><creatorcontrib>Wiersinga, W. Joost</creatorcontrib><creatorcontrib>Wuthiekanun, Vanaporn</creatorcontrib><creatorcontrib>Lee, Sue J.</creatorcontrib><creatorcontrib>Mahavanakul, Weera</creatorcontrib><creatorcontrib>Chaowagul, Wipada</creatorcontrib><creatorcontrib>Chierakul, Wirongrong</creatorcontrib><creatorcontrib>White, Nicholas J.</creatorcontrib><creatorcontrib>van der Poll, Tom</creatorcontrib><creatorcontrib>Day, Nicholas P. J.</creatorcontrib><creatorcontrib>Dougan, Gordon</creatorcontrib><creatorcontrib>Peacock, Sharon J.</creatorcontrib><title>Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K ATP -channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, incljuding inhibition of inflammasome assembly and would be predicted to influence the host response to infection. Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system.</description><subject>ABC transporters</subject><subject>Adult</subject><subject>and Commentaries</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Antiinflammatories</subject><subject>ARTICLES AND COMMENTARIES</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Burkholderia pseudomallei - isolation & purification</subject><subject>Cohort Studies</subject><subject>Correlation analysis</subject><subject>Diabetes</subject><subject>Diabetes complications</subject><subject>Female</subject><subject>Gene expression</subject><subject>Glyburide - administration & dosage</subject><subject>Gram-negative bacteria</subject><subject>Hospital admissions</subject><subject>Human bacterial diseases</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Leukocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Melioidosis</subject><subject>Melioidosis - drug therapy</subject><subject>Melioidosis - mortality</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neutrophils</subject><subject>Prospective Studies</subject><subject>Sepsis</subject><subject>Sepsis - drug therapy</subject><subject>Sepsis - microbiology</subject><subject>Sepsis - mortality</subject><subject>Survival Analysis</subject><subject>Treatment Outcome</subject><subject>Tropical bacterial diseases</subject><subject>Type 2 diabetes mellitus</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kttrFDEUxoMotq6--K4MBVGE0VwnkxdhKfYCLYKX55DJxWbJTLZJRtn_3iy7vdiHPoQk5Mf3nXO-APAawU8ICvJZe1PXNRL4CThEjPC2YwI9rWfI-pb2pD8AL3JeQYhQD9lzcIARFgRSfgh-nIbNMCdvbHOem-VUfOsnF9Q4qhLTplGTaZY5R-1Vsab568tV892aWdfLZUxFBV82jZ-aSxt89CZmn1-CZ06FbF_t9wX4dfL15_FZe_Ht9Px4edFqhkRpB6yY65B2VCk8EGRINzgHO-GEI1hYBpkRQhjuNLeUi4E6KGCHKeRYcYfIAnzZ6a7nYbRG26kkFeQ6-VGljYzKy_9fJn8lf8c_srYuCN0KvN8LpHg921zk6LO2IajJxjnLnjEMRV9nvAAfHiUR511HOYOwokcP0FWc01QHUfU4Rh1hW-ePO0inmHOy7rZqBOU2VFlDlbtQK_z2fp-36E2KFXi3B1TWKrikJu3zHUehqK73uDivHzd8s-NWuX6COx3BOSc9Jv8AIlXBQQ</recordid><startdate>20110315</startdate><enddate>20110315</enddate><creator>Koh, Gavin C. K. W.</creator><creator>Maude, Rapeephan R.</creator><creator>Schreiber, M. Fernanda</creator><creator>Limmathurotsakul, Direk</creator><creator>Wiersinga, W. Joost</creator><creator>Wuthiekanun, Vanaporn</creator><creator>Lee, Sue J.</creator><creator>Mahavanakul, Weera</creator><creator>Chaowagul, Wipada</creator><creator>Chierakul, Wirongrong</creator><creator>White, Nicholas J.</creator><creator>van der Poll, Tom</creator><creator>Day, Nicholas P. J.</creator><creator>Dougan, Gordon</creator><creator>Peacock, Sharon J.</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T2</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110315</creationdate><title>Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis</title><author>Koh, Gavin C. K. W. ; Maude, Rapeephan R. ; Schreiber, M. Fernanda ; Limmathurotsakul, Direk ; Wiersinga, W. Joost ; Wuthiekanun, Vanaporn ; Lee, Sue J. ; Mahavanakul, Weera ; Chaowagul, Wipada ; Chierakul, Wirongrong ; White, Nicholas J. ; van der Poll, Tom ; Day, Nicholas P. 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J.</creatorcontrib><creatorcontrib>Dougan, Gordon</creatorcontrib><creatorcontrib>Peacock, Sharon J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Koh, Gavin C. K. W.</au><au>Maude, Rapeephan R.</au><au>Schreiber, M. Fernanda</au><au>Limmathurotsakul, Direk</au><au>Wiersinga, W. Joost</au><au>Wuthiekanun, Vanaporn</au><au>Lee, Sue J.</au><au>Mahavanakul, Weera</au><au>Chaowagul, Wipada</au><au>Chierakul, Wirongrong</au><au>White, Nicholas J.</au><au>van der Poll, Tom</au><au>Day, Nicholas P. J.</au><au>Dougan, Gordon</au><au>Peacock, Sharon J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2011-03-15</date><risdate>2011</risdate><volume>52</volume><issue>6</issue><spage>717</spage><epage>725</epage><pages>717-725</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><abstract>Background. Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K ATP -channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, incljuding inhibition of inflammasome assembly and would be predicted to influence the host response to infection. Methods. We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea. Results. Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group. Conclusions. We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>21293047</pmid><doi>10.1093/cid/ciq192</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical infectious diseases, 2011-03, Vol.52 (6), p.717-725 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | ABC transporters Adult and Commentaries Anti-Inflammatory Agents - administration & dosage Antiinflammatories ARTICLES AND COMMENTARIES Bacterial diseases Biological and medical sciences Burkholderia pseudomallei - isolation & purification Cohort Studies Correlation analysis Diabetes Diabetes complications Female Gene expression Glyburide - administration & dosage Gram-negative bacteria Hospital admissions Human bacterial diseases Humans Immune system Infections Infectious diseases Leukocytes Male Medical sciences Melioidosis Melioidosis - drug therapy Melioidosis - mortality Middle Aged Mortality Neutrophils Prospective Studies Sepsis Sepsis - drug therapy Sepsis - microbiology Sepsis - mortality Survival Analysis Treatment Outcome Tropical bacterial diseases Type 2 diabetes mellitus |
| title | Glyburide Is Anti-inflammatory and Associated with Reduced Mortality in Melioidosis |
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