Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients
Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well establis...
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| Veröffentlicht in: | PloS one 2014-07, Vol.9 (7), p.e100446-e100446 |
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| creator | Chen, Jun Shao, Jiasheng Cai, Rentian Shen, Yinzhong Zhang, Renfang Liu, Li Qi, Tangkai Lu, Hongzhou |
| description | Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.
We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).
Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P |
| doi_str_mv | 10.1371/journal.pone.0100446 |
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We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).
Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.
IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0100446</identifier><identifier>PMID: 24983463</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Anti-Retroviral Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Catabolites ; CD14 antigen ; CD4 antigen ; CD4 Lymphocyte Count ; Dendritic cells ; Drug therapy ; Female ; Health care ; Highly active antiretroviral therapy ; HIV ; HIV infections ; HIV Infections - drug therapy ; HIV Infections - metabolism ; HIV patients ; Human immunodeficiency virus ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Infections ; Infectious diseases ; Kynurenine - blood ; Kynurenine - metabolism ; Lipopolysaccharide Receptors - blood ; Lymphocytes T ; Male ; Measurement methods ; Medicine and health sciences ; Microorganisms ; Mortality ; Pathogenesis ; Pathogens ; Patients ; Public health ; T cells ; Therapy ; Translocation ; Tryptophan ; Tryptophan - blood ; Tryptophan - metabolism ; Tryptophan 2,3-dioxygenase</subject><ispartof>PloS one, 2014-07, Vol.9 (7), p.e100446-e100446</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Chen et al 2014 Chen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-1632fdb3622d25d90b28ca67cb779c5629d542b97d5041e9d84c32796a0daa3c3</citedby><cites>FETCH-LOGICAL-c692t-1632fdb3622d25d90b28ca67cb779c5629d542b97d5041e9d84c32796a0daa3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077698/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077698/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24983463$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Jun</creatorcontrib><creatorcontrib>Shao, Jiasheng</creatorcontrib><creatorcontrib>Cai, Rentian</creatorcontrib><creatorcontrib>Shen, Yinzhong</creatorcontrib><creatorcontrib>Zhang, Renfang</creatorcontrib><creatorcontrib>Liu, Li</creatorcontrib><creatorcontrib>Qi, Tangkai</creatorcontrib><creatorcontrib>Lu, Hongzhou</creatorcontrib><title>Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.
We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).
Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.
IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.</description><subject>Adult</subject><subject>Anti-Retroviral Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Catabolites</subject><subject>CD14 antigen</subject><subject>CD4 antigen</subject><subject>CD4 Lymphocyte Count</subject><subject>Dendritic cells</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Health care</subject><subject>Highly active antiretroviral therapy</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - drug therapy</subject><subject>HIV Infections - metabolism</subject><subject>HIV patients</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Kynurenine - blood</subject><subject>Kynurenine - metabolism</subject><subject>Lipopolysaccharide Receptors - blood</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Measurement methods</subject><subject>Medicine and health sciences</subject><subject>Microorganisms</subject><subject>Mortality</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Patients</subject><subject>Public health</subject><subject>T cells</subject><subject>Therapy</subject><subject>Translocation</subject><subject>Tryptophan</subject><subject>Tryptophan - blood</subject><subject>Tryptophan - metabolism</subject><subject>Tryptophan 2,3-dioxygenase</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk2-L1DAQxoso3rn6DUQLgijYNU3StH0jLId6CwcH_rm3IU2mu1naZE3S5dZPb9btHVu5F1JCQ_p7nsnMdJLkZY7mOSnzjxs7OCO6-dYamKMcIUrZo-Q8rwnOGEbk8cn-LHnm_QahglSMPU3OMK0rQhk5T3YLE3TmIDi70050aViDE9t9qkA6EB582gwhVTZujA1xuV50-jek2ijbgei1gRR_IJnS9na_AhM1qZBB73TYRyi9XN5k2rQgA6h0K4IGE_zz5EkrOg8vxvcs-fnl84-Ly-zq-uvyYnGVSVbjkOWM4FY1hGGscKFq1OBKClbKpixrWTBcq4Lipi5VgWgOtaqoJLismUBKCCLJLHl99N121vOxZJ7nUYVoLAeJxPJIKCs2fOt0L9yeW6H53wPrVly4oGUHXLSKAakQQ4jQpmW1ZKTNWS5UGwODiF6fxmhD04OSMdNY0onp9IvRa76yO05RWbLYklnybjRw9tcAPvBeewldJwzY4XhvVqC6whF98w_6cHYjtRIxgdgGG-PKgylf0JyxsqzwwWv-ABUfBb2W8f9qdTyfCN5PBJEJcBtWYvCeL79_-3_2-mbKvj1h1yC6sPa2G4K2xk9BegSls947aO-LnCN-GI-7avDDePBxPKLs1WmD7kV380D-AFX5C0g</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Chen, Jun</creator><creator>Shao, Jiasheng</creator><creator>Cai, Rentian</creator><creator>Shen, Yinzhong</creator><creator>Zhang, Renfang</creator><creator>Liu, Li</creator><creator>Qi, Tangkai</creator><creator>Lu, Hongzhou</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140701</creationdate><title>Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients</title><author>Chen, Jun ; Shao, Jiasheng ; Cai, Rentian ; Shen, Yinzhong ; Zhang, Renfang ; Liu, Li ; Qi, Tangkai ; Lu, Hongzhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-1632fdb3622d25d90b28ca67cb779c5629d542b97d5041e9d84c32796a0daa3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Anti-Retroviral Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Jun</au><au>Shao, Jiasheng</au><au>Cai, Rentian</au><au>Shen, Yinzhong</au><au>Zhang, Renfang</au><au>Liu, Li</au><au>Qi, Tangkai</au><au>Lu, Hongzhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>9</volume><issue>7</issue><spage>e100446</spage><epage>e100446</epage><pages>e100446-e100446</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.
We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).
Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.
IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24983463</pmid><doi>10.1371/journal.pone.0100446</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Anti-Retroviral Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Catabolites CD14 antigen CD4 antigen CD4 Lymphocyte Count Dendritic cells Drug therapy Female Health care Highly active antiretroviral therapy HIV HIV infections HIV Infections - drug therapy HIV Infections - metabolism HIV patients Human immunodeficiency virus Humans Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Infections Infectious diseases Kynurenine - blood Kynurenine - metabolism Lipopolysaccharide Receptors - blood Lymphocytes T Male Measurement methods Medicine and health sciences Microorganisms Mortality Pathogenesis Pathogens Patients Public health T cells Therapy Translocation Tryptophan Tryptophan - blood Tryptophan - metabolism Tryptophan 2,3-dioxygenase |
| title | Anti-retroviral therapy decreases but does not normalize indoleamine 2,3-dioxygenase activity in HIV-infected patients |
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