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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Veröffentlicht in:Journal of viral hepatitis 2012-07, Vol.19 (7), p.501-508
Hauptverfasser: Warshow, U. M., Riva, A., Hegazy, D., Thurairajah, P. H., Kaminski, E.R., Chokshi, S., Cramp, M. E.
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container_end_page 508
container_issue 7
container_start_page 501
container_title Journal of viral hepatitis
container_volume 19
creator Warshow, U. M.
Riva, A.
Hegazy, D.
Thurairajah, P. H.
Kaminski, E.R.
Chokshi, S.
Cramp, M. E.
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 
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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 &lt; 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. 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Cytokine profiling demonstrated raised levels of pro‐inflammatory innate immune cytokines and chemokines in EU IDU, in particular interleukin‐6 and interleukin‐8. 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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 &lt; 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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