Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-γ production, and expansion of natural killer cells
We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis r...
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Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2001-02, Vol.61 (3), p.884-888 |
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creator | SON, Young-Ik DALLAL, Ramsey M MAILLIARD, Robbie B EGAWA, Shinichi JONAK, Zdenka L LOTZE, Michael T |
description | We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo. |
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The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 11221875</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Division - drug effects ; Cytotoxicity, Immunologic - drug effects ; Drug Synergism ; Humans ; Immunotherapy ; Interferon-gamma - biosynthesis ; Interleukin-18 - pharmacology ; Interleukin-2 - pharmacology ; Killer Cells, Natural - drug effects ; Killer Cells, Natural - immunology ; Killer Cells, Natural - metabolism ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Lymphocyte Activation - drug effects ; Lymphocytes - drug effects ; Lymphocytes - immunology ; Lymphocytes - metabolism ; Lymphoma, B-Cell - immunology ; Medical sciences ; Pharmacology. Drug treatments ; Receptors, Interleukin-2 - biosynthesis ; Tumor Cells, Cultured ; Up-Regulation - drug effects</subject><ispartof>Cancer research (Chicago, Ill.), 2001-02, Vol.61 (3), p.884-888</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=896503$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11221875$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SON, Young-Ik</creatorcontrib><creatorcontrib>DALLAL, Ramsey M</creatorcontrib><creatorcontrib>MAILLIARD, Robbie B</creatorcontrib><creatorcontrib>EGAWA, Shinichi</creatorcontrib><creatorcontrib>JONAK, Zdenka L</creatorcontrib><creatorcontrib>LOTZE, Michael T</creatorcontrib><title>Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-γ production, and expansion of natural killer cells</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Cytotoxicity, Immunologic - drug effects</subject><subject>Drug Synergism</subject><subject>Humans</subject><subject>Immunotherapy</subject><subject>Interferon-gamma - biosynthesis</subject><subject>Interleukin-18 - pharmacology</subject><subject>Interleukin-2 - pharmacology</subject><subject>Killer Cells, Natural - drug effects</subject><subject>Killer Cells, Natural - immunology</subject><subject>Killer Cells, Natural - metabolism</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Lymphocytes - drug effects</subject><subject>Lymphocytes - immunology</subject><subject>Lymphocytes - metabolism</subject><subject>Lymphoma, B-Cell - immunology</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Receptors, Interleukin-2 - biosynthesis</subject><subject>Tumor Cells, Cultured</subject><subject>Up-Regulation - drug effects</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kN9KwzAYxYMobk5fQQLeKKyQNE2bXsrwz2DgjV6PNPni4rK0JClar30j38NnsuL06nAOv-_A-Q7QlHImsqoo-CGaEkJExosqn6CTGF9Gyynhx2hCaZ5TUfEp-lj6BMFBv7U-owJfLlejXOE4eAjP9h0ifrVpg8c4x6nF4DfSK8BqSG1q36yyaZhj-1NiILQ--_rEXWh1r5Jt_RxLrzG8ddLH0eLWYC9TH6TDW-scBKzAuXiKjox0Ec72OkNPtzePi_ts9XC3XFyvsi5nPGWsElUDRhvCSkXrRhWCi4JIUhqloSCclw0ttDE5JzXTdQOQl-ORZBpYaSo2Q-e_vV3f7ECvu2B3Mgzrv3eMwMUekFFJZ8K41cZ_TtQlJ4x9A9jqayQ</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>SON, Young-Ik</creator><creator>DALLAL, Ramsey M</creator><creator>MAILLIARD, Robbie B</creator><creator>EGAWA, Shinichi</creator><creator>JONAK, Zdenka L</creator><creator>LOTZE, Michael T</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>20010201</creationdate><title>Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-γ production, and expansion of natural killer cells</title><author>SON, Young-Ik ; DALLAL, Ramsey M ; MAILLIARD, Robbie B ; EGAWA, Shinichi ; JONAK, Zdenka L ; LOTZE, Michael T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p235t-3787befdf036c19bc485840a06fcde40556b14dff25093d9bee26378a3de36f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>CD4-Positive T-Lymphocytes - drug effects</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Cytotoxicity, Immunologic - drug effects</topic><topic>Drug Synergism</topic><topic>Humans</topic><topic>Immunotherapy</topic><topic>Interferon-gamma - biosynthesis</topic><topic>Interleukin-18 - pharmacology</topic><topic>Interleukin-2 - pharmacology</topic><topic>Killer Cells, Natural - drug effects</topic><topic>Killer Cells, Natural - immunology</topic><topic>Killer Cells, Natural - metabolism</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Lymphocyte Activation - drug effects</topic><topic>Lymphocytes - drug effects</topic><topic>Lymphocytes - immunology</topic><topic>Lymphocytes - metabolism</topic><topic>Lymphoma, B-Cell - immunology</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Receptors, Interleukin-2 - biosynthesis</topic><topic>Tumor Cells, Cultured</topic><topic>Up-Regulation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SON, Young-Ik</creatorcontrib><creatorcontrib>DALLAL, Ramsey M</creatorcontrib><creatorcontrib>MAILLIARD, Robbie B</creatorcontrib><creatorcontrib>EGAWA, Shinichi</creatorcontrib><creatorcontrib>JONAK, Zdenka L</creatorcontrib><creatorcontrib>LOTZE, Michael T</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SON, Young-Ik</au><au>DALLAL, Ramsey M</au><au>MAILLIARD, Robbie B</au><au>EGAWA, Shinichi</au><au>JONAK, Zdenka L</au><au>LOTZE, Michael T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-γ production, and expansion of natural killer cells</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2001-02-01</date><risdate>2001</risdate><volume>61</volume><issue>3</issue><spage>884</spage><epage>888</epage><pages>884-888</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>We investigated the in vitro effects of combining interleukin-18 (IL-18) and IL-2 on human lymphocytes. The combined use of these two cytokines synergistically enhanced the proliferation, cytolytic activity, and interferon-gamma production of peripheral blood mononuclear cells. Phenotypic analysis revealed a preferential expansion of CD56+CD3- cells and an up-regulation of IL-2 receptor-alpha expression on natural killer cells. Isolated natural killer cells showed a substantial increase in proliferation and cytotoxicity compared with CD4+ and CD8+ T cells. The combined use of IL-18 and IL-2 should be considered a viable strategy to induce an antitumor response in vivo.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11221875</pmid><tpages>5</tpages></addata></record> |
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source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals |
subjects | Antineoplastic agents Biological and medical sciences CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Division - drug effects Cytotoxicity, Immunologic - drug effects Drug Synergism Humans Immunotherapy Interferon-gamma - biosynthesis Interleukin-18 - pharmacology Interleukin-2 - pharmacology Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Killer Cells, Natural - metabolism Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Lymphocyte Activation - drug effects Lymphocytes - drug effects Lymphocytes - immunology Lymphocytes - metabolism Lymphoma, B-Cell - immunology Medical sciences Pharmacology. Drug treatments Receptors, Interleukin-2 - biosynthesis Tumor Cells, Cultured Up-Regulation - drug effects |
title | Interleukin-18 (IL-18) synergizes with IL-2 to enhance cytotoxicity, interferon-γ production, and expansion of natural killer cells |
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