Immune dysregulation in severe influenza
Among previously healthy children with severe influenza, the mechanisms leading to increased pathology are not understood. We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined pl...
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| Veröffentlicht in: | Journal of leukocyte biology 2009-06, Vol.85 (6), p.1036-1043 |
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| container_title | Journal of leukocyte biology |
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| creator | Heltzer, Meredith L. Coffin, Susan E. Maurer, Kelly Bagashev, Asen Zhang, Zhe Orange, Jordan S. Sullivan, Kathleen E. |
| description | Among previously healthy children with severe influenza, the mechanisms leading to increased pathology are not understood. We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005–2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P |
| doi_str_mv | 10.1189/jlb.1108710 |
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We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005–2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P<0.05). These normalized when retested during a convalescent phase. Plasma levels of IL‐6, IL‐12, and IFN‐γ were elevated in influenza patients compared with controls (P<0.05). A compromised ability to produce TNF‐α was reproduced by in vitro infection, and the magnitude of the effect correlated with the multiplicity of infection and induction of IFN regulatory factor 4 expression. Aberrant, systemic, innate responses to TLR ligands during influenza infection may be a consequence of specific viral attributes such as a high inoculum or rapid replication and may underlie the known susceptibility of influenza‐infected patients to secondary bacterial infections.</description><identifier>ISSN: 0741-5400</identifier><identifier>EISSN: 1938-3673</identifier><identifier>DOI: 10.1189/jlb.1108710</identifier><identifier>PMID: 19276177</identifier><language>eng</language><publisher>United States: Society for Leukocyte Biology</publisher><subject>Blotting, Western ; Child, Preschool ; Children ; Cytokines ; Cytokines - blood ; Female ; Flow Cytometry ; g-Interferon ; Gene Expression Regulation ; Host Defense and Pathophysiology ; Humans ; IFN ; IL‐6 ; Immune System Diseases - complications ; Immune System Diseases - immunology ; Immune System Diseases - physiopathology ; Infant ; Influenza ; Influenza, Human - complications ; Influenza, Human - genetics ; Influenza, Human - immunology ; Influenza, Human - physiopathology ; Inoculum ; Interferon ; Interferon Regulatory Factors - metabolism ; Interleukin 12 ; Interleukin 6 ; IRF4 ; Killer Cells, Natural - immunology ; Killer Cells, Natural - virology ; Leukocytes ; Leukocytes, Mononuclear - virology ; Male ; Multiplicity of infection ; Natural Cytotoxicity Triggering Receptor 1 - immunology ; Natural killer cells ; NK cells ; NKp46 ; Peripheral blood ; Plasma levels ; Replication ; Respiratory syncytial virus ; TLR ; Toll-Like Receptors - metabolism ; Tumor necrosis factor-a</subject><ispartof>Journal of leukocyte biology, 2009-06, Vol.85 (6), p.1036-1043</ispartof><rights>2009 Society for Leukocyte Biology</rights><rights>2009 Society for Leukocyte Biology 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4826-4dffdbeda66853e863b9c5141a39f0bbcc4945f409e1f1920ff0f88726d910273</citedby><cites>FETCH-LOGICAL-c4826-4dffdbeda66853e863b9c5141a39f0bbcc4945f409e1f1920ff0f88726d910273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1189%2Fjlb.1108710$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1189%2Fjlb.1108710$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,777,781,882,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19276177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heltzer, Meredith L.</creatorcontrib><creatorcontrib>Coffin, Susan E.</creatorcontrib><creatorcontrib>Maurer, Kelly</creatorcontrib><creatorcontrib>Bagashev, Asen</creatorcontrib><creatorcontrib>Zhang, Zhe</creatorcontrib><creatorcontrib>Orange, Jordan S.</creatorcontrib><creatorcontrib>Sullivan, Kathleen E.</creatorcontrib><title>Immune dysregulation in severe influenza</title><title>Journal of leukocyte biology</title><addtitle>J Leukoc Biol</addtitle><description>Among previously healthy children with severe influenza, the mechanisms leading to increased pathology are not understood. We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005–2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P<0.05). These normalized when retested during a convalescent phase. Plasma levels of IL‐6, IL‐12, and IFN‐γ were elevated in influenza patients compared with controls (P<0.05). A compromised ability to produce TNF‐α was reproduced by in vitro infection, and the magnitude of the effect correlated with the multiplicity of infection and induction of IFN regulatory factor 4 expression. Aberrant, systemic, innate responses to TLR ligands during influenza infection may be a consequence of specific viral attributes such as a high inoculum or rapid replication and may underlie the known susceptibility of influenza‐infected patients to secondary bacterial infections.</description><subject>Blotting, Western</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>g-Interferon</subject><subject>Gene Expression Regulation</subject><subject>Host Defense and Pathophysiology</subject><subject>Humans</subject><subject>IFN</subject><subject>IL‐6</subject><subject>Immune System Diseases - complications</subject><subject>Immune System Diseases - immunology</subject><subject>Immune System Diseases - physiopathology</subject><subject>Infant</subject><subject>Influenza</subject><subject>Influenza, Human - complications</subject><subject>Influenza, Human - genetics</subject><subject>Influenza, Human - immunology</subject><subject>Influenza, Human - physiopathology</subject><subject>Inoculum</subject><subject>Interferon</subject><subject>Interferon Regulatory Factors - metabolism</subject><subject>Interleukin 12</subject><subject>Interleukin 6</subject><subject>IRF4</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - virology</subject><subject>Leukocytes</subject><subject>Leukocytes, Mononuclear - virology</subject><subject>Male</subject><subject>Multiplicity of infection</subject><subject>Natural Cytotoxicity Triggering Receptor 1 - immunology</subject><subject>Natural killer cells</subject><subject>NK cells</subject><subject>NKp46</subject><subject>Peripheral blood</subject><subject>Plasma levels</subject><subject>Replication</subject><subject>Respiratory syncytial virus</subject><subject>TLR</subject><subject>Toll-Like Receptors - metabolism</subject><subject>Tumor necrosis factor-a</subject><issn>0741-5400</issn><issn>1938-3673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1P3DAQxa0KVLa0p96rPaFKVWDsOP64IFHUD9BKvbRny0nGu0ZOAvZmo-1fj2FXpVzg5JH805s37xHykcIppUqf3YQ6D6AkhTdkRnWpilLI8oDMQHJaVBzgiLxL6QYASibgLTmimklBpZyRz1ddN_Y4b7cp4nIMdu2Hfu77ecINRsyTCyP2f-17cuhsSPhh_x6TP9-__b78WSx-_bi6vFgUDVdMFLx1rq2xtUKoqkQlylo3FeXUltpBXTcN17xyHDRSl22Ac-CUkky0mgKT5TE53-nejnWHbYP9OtpgbqPvbNyawXrz_Kf3K7McNoYJrSqlssDJXiAOdyOmtel8ajAE2-MwJpOjYRSq6lWQgZaglM7glx3YxCHlmNw_NxTMQwUmV2D2FWT60_8HPLH7zDMAO2DyAbcvaZnrxdesKJ6srvxyNfmIJnU2hLyBmWmaVGWEeQTvAVp3nes</recordid><startdate>200906</startdate><enddate>200906</enddate><creator>Heltzer, Meredith L.</creator><creator>Coffin, Susan E.</creator><creator>Maurer, Kelly</creator><creator>Bagashev, Asen</creator><creator>Zhang, Zhe</creator><creator>Orange, Jordan S.</creator><creator>Sullivan, Kathleen E.</creator><general>Society for Leukocyte Biology</general><general>The Society for Leukocyte Biology</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>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200906</creationdate><title>Immune dysregulation in severe influenza</title><author>Heltzer, Meredith L. ; 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We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005–2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P<0.05). These normalized when retested during a convalescent phase. Plasma levels of IL‐6, IL‐12, and IFN‐γ were elevated in influenza patients compared with controls (P<0.05). A compromised ability to produce TNF‐α was reproduced by in vitro infection, and the magnitude of the effect correlated with the multiplicity of infection and induction of IFN regulatory factor 4 expression. Aberrant, systemic, innate responses to TLR ligands during influenza infection may be a consequence of specific viral attributes such as a high inoculum or rapid replication and may underlie the known susceptibility of influenza‐infected patients to secondary bacterial infections.</abstract><cop>United States</cop><pub>Society for Leukocyte Biology</pub><pmid>19276177</pmid><doi>10.1189/jlb.1108710</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Blotting, Western Child, Preschool Children Cytokines Cytokines - blood Female Flow Cytometry g-Interferon Gene Expression Regulation Host Defense and Pathophysiology Humans IFN IL‐6 Immune System Diseases - complications Immune System Diseases - immunology Immune System Diseases - physiopathology Infant Influenza Influenza, Human - complications Influenza, Human - genetics Influenza, Human - immunology Influenza, Human - physiopathology Inoculum Interferon Interferon Regulatory Factors - metabolism Interleukin 12 Interleukin 6 IRF4 Killer Cells, Natural - immunology Killer Cells, Natural - virology Leukocytes Leukocytes, Mononuclear - virology Male Multiplicity of infection Natural Cytotoxicity Triggering Receptor 1 - immunology Natural killer cells NK cells NKp46 Peripheral blood Plasma levels Replication Respiratory syncytial virus TLR Toll-Like Receptors - metabolism Tumor necrosis factor-a |
| title | Immune dysregulation in severe influenza |
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