Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection
A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanis...
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description | A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment‐naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV‐Ab+ and HCV‐RNA−) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL‐6 (on average more than 100‐fold, P = 0.001) and IL‐8 (on average more than 10‐fold, P |
doi_str_mv | 10.1111/j.1365-2893.2011.01574.x |
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M. ; Riva, A. ; Hegazy, D. ; Thurairajah, P. H. ; Kaminski, E.R. ; Chokshi, S. ; Cramp, M. E.</creator><creatorcontrib>Warshow, U. M. ; Riva, A. ; Hegazy, D. ; Thurairajah, P. H. ; Kaminski, E.R. ; Chokshi, S. ; Cramp, M. E.</creatorcontrib><description>A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment‐naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV‐Ab+ and HCV‐RNA−) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL‐6 (on average more than 100‐fold, P = 0.001) and IL‐8 (on average more than 10‐fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor‐alpha (TNF‐α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon‐alpha (IFN‐α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro‐inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin‐6 and interleukin‐8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort.</description><identifier>ISSN: 1352-0504</identifier><identifier>EISSN: 1365-2893</identifier><identifier>DOI: 10.1111/j.1365-2893.2011.01574.x</identifier><identifier>PMID: 22676363</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; chemokines ; Cohort Studies ; cytokines ; Cytokines - blood ; Disease Resistance ; exposed uninfecteds ; Female ; Hepatitis C - immunology ; Hepatitis C - prevention & control ; hepatitis C virus ; Humans ; injection drug users ; interleukins ; Male ; Needle Sharing ; Substance Abuse, Intravenous - complications ; Substance Abuse, Intravenous - immunology</subject><ispartof>Journal of viral hepatitis, 2012-07, Vol.19 (7), p.501-508</ispartof><rights>2012 Blackwell Publishing Ltd</rights><rights>2012 Blackwell Publishing Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4074-8f9856ed01ce11b504bf36f3ce6c6cd9855a3571f345cb4c58f4431fb2fc44d93</citedby><cites>FETCH-LOGICAL-c4074-8f9856ed01ce11b504bf36f3ce6c6cd9855a3571f345cb4c58f4431fb2fc44d93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2893.2011.01574.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2893.2011.01574.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22676363$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Warshow, U. M.</creatorcontrib><creatorcontrib>Riva, A.</creatorcontrib><creatorcontrib>Hegazy, D.</creatorcontrib><creatorcontrib>Thurairajah, P. H.</creatorcontrib><creatorcontrib>Kaminski, E.R.</creatorcontrib><creatorcontrib>Chokshi, S.</creatorcontrib><creatorcontrib>Cramp, M. E.</creatorcontrib><title>Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection</title><title>Journal of viral hepatitis</title><addtitle>J Viral Hepat</addtitle><description>A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment‐naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV‐Ab+ and HCV‐RNA−) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL‐6 (on average more than 100‐fold, P = 0.001) and IL‐8 (on average more than 10‐fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor‐alpha (TNF‐α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon‐alpha (IFN‐α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro‐inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin‐6 and interleukin‐8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort.</description><subject>Adult</subject><subject>chemokines</subject><subject>Cohort Studies</subject><subject>cytokines</subject><subject>Cytokines - blood</subject><subject>Disease Resistance</subject><subject>exposed uninfecteds</subject><subject>Female</subject><subject>Hepatitis C - immunology</subject><subject>Hepatitis C - prevention & control</subject><subject>hepatitis C virus</subject><subject>Humans</subject><subject>injection drug users</subject><subject>interleukins</subject><subject>Male</subject><subject>Needle Sharing</subject><subject>Substance Abuse, Intravenous - complications</subject><subject>Substance Abuse, Intravenous - immunology</subject><issn>1352-0504</issn><issn>1365-2893</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUcuOEzEQHCEQ-4BfQD5ymcEeP2Zy4IAiNstqBWIFLOJieTztxEnmge1Zkk_hb7GZJWd8cbe6qlpdlWWI4ILE92ZbECp4XtYLWpSYkAITXrHi8CQ7Pw2eppqXOeaYnWUX3m8xJrTk5Hl2VpaiElTQ8-z38hiGne0BjW4wdg8e2R5t7HqDnPW72GxBBzv0qHXTGk0enEd-Wq_BhwTtVQCkPBrGcfDQojAg1aox2AdAtuum3oZjUlTjqBz0ATnw1gfVa0jYDYwq2GA9WqIH66YkaeaFL7JnRu09vHz8L7OvV--_LK_z20-rD8t3t7lmuGJ5bRY1F9BiooGQJh7bGCoM1SC00G0cckV5RQxlXDdM89owRolpSqMZaxf0Mns960YDfk7xLNlZr2G_Vz0Mk5cEk4UgjHIWofUM1W7w3oGRo7OdcscIkikYuZXJf5n8lykY-TcYeYjUV49bpqaD9kT8l0QEvJ0Bv2IIx_8WljffrlMV-fnMj-7C4cRXbidFRSsu7z-uZH13v_r84-pOfqd_AKTfr4g</recordid><startdate>201207</startdate><enddate>201207</enddate><creator>Warshow, U. M.</creator><creator>Riva, A.</creator><creator>Hegazy, D.</creator><creator>Thurairajah, P. H.</creator><creator>Kaminski, E.R.</creator><creator>Chokshi, S.</creator><creator>Cramp, M. E.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>201207</creationdate><title>Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection</title><author>Warshow, U. M. ; Riva, A. ; Hegazy, D. ; Thurairajah, P. H. ; Kaminski, E.R. ; Chokshi, S. ; Cramp, M. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4074-8f9856ed01ce11b504bf36f3ce6c6cd9855a3571f345cb4c58f4431fb2fc44d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>chemokines</topic><topic>Cohort Studies</topic><topic>cytokines</topic><topic>Cytokines - blood</topic><topic>Disease Resistance</topic><topic>exposed uninfecteds</topic><topic>Female</topic><topic>Hepatitis C - immunology</topic><topic>Hepatitis C - prevention & control</topic><topic>hepatitis C virus</topic><topic>Humans</topic><topic>injection drug users</topic><topic>interleukins</topic><topic>Male</topic><topic>Needle Sharing</topic><topic>Substance Abuse, Intravenous - complications</topic><topic>Substance Abuse, Intravenous - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Warshow, U. M.</creatorcontrib><creatorcontrib>Riva, A.</creatorcontrib><creatorcontrib>Hegazy, D.</creatorcontrib><creatorcontrib>Thurairajah, P. H.</creatorcontrib><creatorcontrib>Kaminski, E.R.</creatorcontrib><creatorcontrib>Chokshi, S.</creatorcontrib><creatorcontrib>Cramp, M. E.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of viral hepatitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Warshow, U. M.</au><au>Riva, A.</au><au>Hegazy, D.</au><au>Thurairajah, P. H.</au><au>Kaminski, E.R.</au><au>Chokshi, S.</au><au>Cramp, M. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection</atitle><jtitle>Journal of viral hepatitis</jtitle><addtitle>J Viral Hepat</addtitle><date>2012-07</date><risdate>2012</risdate><volume>19</volume><issue>7</issue><spage>501</spage><epage>508</epage><pages>501-508</pages><issn>1352-0504</issn><eissn>1365-2893</eissn><abstract>A cohort of injection drug users (IDU) have been identified who despite a long history of IDU and sharing of injecting equipment remain seronegative and aviraemic for hepatitis C virus (HCV). They have been termed HCV exposed uninfected (EU). The study of potential innate or adaptive immune mechanisms of resistance to HCV infection in this group is of interest. The aim of this study was to determine the levels of a broad range of cytokines in serum of exposed, uninfected individuals to ascertain whether there is a specific cytokine profile associated with apparent resistance to HCV. Sera from 22 EU individuals were analysed for a range of cytokines and chemokines, and compared to 16 treatment‐naive chronic HCV cases (HCV Ab+ RNA+), 16 individuals with spontaneous resolution of HCV (HCV‐Ab+ and HCV‐RNA−) and 10 healthy unexposed controls. EU subjects had strikingly higher levels of both IL‐6 (on average more than 100‐fold, P = 0.001) and IL‐8 (on average more than 10‐fold, P < 0.001) than the comparison groups. Additionally higher levels of tumour necrosis factor‐alpha (TNF‐α; on average up to threefold, P = 0.02) were seen in EU individuals. The levels of interferon‐alpha (IFN‐α) were upregulated in all HCV exposed groups in comparison to healthy controls (P = 0.013). Adaptive immune cytokine levels were no different between the groups. Cytokine profiling demonstrated raised levels of pro‐inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin‐6 and interleukin‐8. These findings suggest innate immune activation may be the key to prevention of infection in this cohort.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22676363</pmid><doi>10.1111/j.1365-2893.2011.01574.x</doi><tpages>8</tpages></addata></record> |
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subjects | Adult chemokines Cohort Studies cytokines Cytokines - blood Disease Resistance exposed uninfecteds Female Hepatitis C - immunology Hepatitis C - prevention & control hepatitis C virus Humans injection drug users interleukins Male Needle Sharing Substance Abuse, Intravenous - complications Substance Abuse, Intravenous - immunology |
title | Cytokine profiles in high risk injection drug users suggests innate as opposed to adaptive immunity in apparent resistance to hepatitis C virus infection |
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