Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock
To analyze the immunomodulatory effect of pyrrolidine dithiocarbamate (PDTC) on the endotoxin (LPS) stimulated inflammatory response, we measured the LPS-stimulated cytokine and NO production in murine peritoneal macrophages, J774A.1 cells and human whole blood in the presence of PDTC (60 μM). PDTC...
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| Veröffentlicht in: | International journal of immunopharmacology 2000, Vol.22 (1), p.83-90 |
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| creator | Meisner, Michael Schmidt, Joachim Schywalsky, Michael Tschaikowsky, Klaus |
| description | To analyze the immunomodulatory effect of pyrrolidine dithiocarbamate (PDTC) on the endotoxin (LPS) stimulated inflammatory response, we measured the LPS-stimulated cytokine and NO production in murine peritoneal macrophages, J774A.1 cells and human whole blood in the presence of PDTC (60 μM). PDTC significantly inhibited the production of nitrite, IL-1β and IL-6 in these cells. TNFα release was stimulated in murine cells, but suppressed in human whole blood. We further investigated the influence of PDTC on mortality and cytokine release in mouse endotoxin shock. PDTC was i.p. injected 30 min prior to the induction of endotoxin shock in female NMRI-mice and survival was significantly improved as compared to controls (48% vs 20%,
n=25 per group). Plasma concentrations of TNFα were slightly augmented while IL-6 levels were decreased in PDTC-treated animals as compared to controls, however, without reaching significance.
We conclude that PDTC is a potent immunomodulatory substance that modulates the inflammatory response in vitro and reduces mortality in mouse endotoxin shock. The pathophysiological mechanisms of the protective effect of PDTC in vivo, however, appears to be pluripotent, comprising both antioxidative properties and the inhibition of NF-kB. |
| doi_str_mv | 10.1016/S0192-0561(99)00071-5 |
| format | Article |
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n=25 per group). Plasma concentrations of TNFα were slightly augmented while IL-6 levels were decreased in PDTC-treated animals as compared to controls, however, without reaching significance.
We conclude that PDTC is a potent immunomodulatory substance that modulates the inflammatory response in vitro and reduces mortality in mouse endotoxin shock. The pathophysiological mechanisms of the protective effect of PDTC in vivo, however, appears to be pluripotent, comprising both antioxidative properties and the inhibition of NF-kB.</description><identifier>ISSN: 0192-0561</identifier><identifier>EISSN: 1879-3495</identifier><identifier>DOI: 10.1016/S0192-0561(99)00071-5</identifier><identifier>PMID: 10684991</identifier><identifier>CODEN: IJIMDS</identifier><language>eng</language><publisher>Oxford: Elsevier Science</publisher><subject>Animals ; Antioxidant ; Antioxidants - pharmacology ; Biological and medical sciences ; Cell Line ; Cytokines ; Cytokines - biosynthesis ; Female ; General and cellular metabolism. Vitamins ; Humans ; Immunomodulation ; Immunomodulators ; Macrophages - drug effects ; Macrophages - immunology ; Medical sciences ; Mice ; Mouse endotoxin shock ; NF-kappa B ; Nitric Oxide - biosynthesis ; PDTC ; Pharmacology. Drug treatments ; Pyrrolidine dithiocarbamate ; Pyrrolidines - pharmacology ; Shock, Septic - drug therapy ; Thiocarbamates - pharmacology ; Thiocarbamates - toxicity</subject><ispartof>International journal of immunopharmacology, 2000, Vol.22 (1), p.83-90</ispartof><rights>2000 International Society for Immunopharmacology</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-a5f849717665290fe22658549643eeb61c458b8053645f49472506fc6e9b40693</citedby><cites>FETCH-LOGICAL-c421t-a5f849717665290fe22658549643eeb61c458b8053645f49472506fc6e9b40693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,4010,27904,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1302366$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10684991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meisner, Michael</creatorcontrib><creatorcontrib>Schmidt, Joachim</creatorcontrib><creatorcontrib>Schywalsky, Michael</creatorcontrib><creatorcontrib>Tschaikowsky, Klaus</creatorcontrib><title>Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock</title><title>International journal of immunopharmacology</title><addtitle>Int J Immunopharmacol</addtitle><description>To analyze the immunomodulatory effect of pyrrolidine dithiocarbamate (PDTC) on the endotoxin (LPS) stimulated inflammatory response, we measured the LPS-stimulated cytokine and NO production in murine peritoneal macrophages, J774A.1 cells and human whole blood in the presence of PDTC (60 μM). PDTC significantly inhibited the production of nitrite, IL-1β and IL-6 in these cells. TNFα release was stimulated in murine cells, but suppressed in human whole blood. We further investigated the influence of PDTC on mortality and cytokine release in mouse endotoxin shock. PDTC was i.p. injected 30 min prior to the induction of endotoxin shock in female NMRI-mice and survival was significantly improved as compared to controls (48% vs 20%,
n=25 per group). Plasma concentrations of TNFα were slightly augmented while IL-6 levels were decreased in PDTC-treated animals as compared to controls, however, without reaching significance.
We conclude that PDTC is a potent immunomodulatory substance that modulates the inflammatory response in vitro and reduces mortality in mouse endotoxin shock. The pathophysiological mechanisms of the protective effect of PDTC in vivo, however, appears to be pluripotent, comprising both antioxidative properties and the inhibition of NF-kB.</description><subject>Animals</subject><subject>Antioxidant</subject><subject>Antioxidants - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cytokines</subject><subject>Cytokines - biosynthesis</subject><subject>Female</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Humans</subject><subject>Immunomodulation</subject><subject>Immunomodulators</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mouse endotoxin shock</subject><subject>NF-kappa B</subject><subject>Nitric Oxide - biosynthesis</subject><subject>PDTC</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrrolidine dithiocarbamate</subject><subject>Pyrrolidines - pharmacology</subject><subject>Shock, Septic - drug therapy</subject><subject>Thiocarbamates - pharmacology</subject><subject>Thiocarbamates - toxicity</subject><issn>0192-0561</issn><issn>1879-3495</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFP5CAYhonR6Kz6EzQcjFkPVWiBlpMxZldNTDyoZ0Lph8NuC13oGOffyziT1Zsnku99PnjzgNARJeeUUHHxSKgsC8IF_SnlGSGkpgXfQjPa1LKomOTbaPYf2UM_UvqTIU5FuYv2KBENk5LOkL_ztl-AN4CDxeMyxtC7znnAnZvmLhgdWz3oKcceT3PALvN6yJMQlzhCGoNPqyketIlhnOsXSFj7Dg9hkQPwXZjCW87TPJi_B2jH6j7B4ebcR8-_fz1d3xb3Dzd311f3hWElnQrNbe5X01oIXkpioSwFbziTglUAraCG8aZtCK8E45ZJVpecCGsEyJYRIat9dLq-d4zh3wLSpAaXDPS99pB7KVpzUlcVzSBfg7l8ShGsGqMbdFwqStRKtPoQrVYWlZTqQ7Tiee9488CiHaD7srU2m4GTDaCT0b2N2huXPrmKlJUQGbtcY5BtvDqIKhm3-o7ORTCT6oL7psk7ViOabQ</recordid><startdate>2000</startdate><enddate>2000</enddate><creator>Meisner, Michael</creator><creator>Schmidt, Joachim</creator><creator>Schywalsky, Michael</creator><creator>Tschaikowsky, Klaus</creator><general>Elsevier Science</general><scope>IQODW</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>7T5</scope><scope>H94</scope></search><sort><creationdate>2000</creationdate><title>Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock</title><author>Meisner, Michael ; Schmidt, Joachim ; Schywalsky, Michael ; Tschaikowsky, Klaus</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-a5f849717665290fe22658549643eeb61c458b8053645f49472506fc6e9b40693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antioxidant</topic><topic>Antioxidants - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cytokines</topic><topic>Cytokines - biosynthesis</topic><topic>Female</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Humans</topic><topic>Immunomodulation</topic><topic>Immunomodulators</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mouse endotoxin shock</topic><topic>NF-kappa B</topic><topic>Nitric Oxide - biosynthesis</topic><topic>PDTC</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrrolidine dithiocarbamate</topic><topic>Pyrrolidines - pharmacology</topic><topic>Shock, Septic - drug therapy</topic><topic>Thiocarbamates - pharmacology</topic><topic>Thiocarbamates - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meisner, Michael</creatorcontrib><creatorcontrib>Schmidt, Joachim</creatorcontrib><creatorcontrib>Schywalsky, Michael</creatorcontrib><creatorcontrib>Tschaikowsky, Klaus</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>International journal of immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meisner, Michael</au><au>Schmidt, Joachim</au><au>Schywalsky, Michael</au><au>Tschaikowsky, Klaus</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock</atitle><jtitle>International journal of immunopharmacology</jtitle><addtitle>Int J Immunopharmacol</addtitle><date>2000</date><risdate>2000</risdate><volume>22</volume><issue>1</issue><spage>83</spage><epage>90</epage><pages>83-90</pages><issn>0192-0561</issn><eissn>1879-3495</eissn><coden>IJIMDS</coden><abstract>To analyze the immunomodulatory effect of pyrrolidine dithiocarbamate (PDTC) on the endotoxin (LPS) stimulated inflammatory response, we measured the LPS-stimulated cytokine and NO production in murine peritoneal macrophages, J774A.1 cells and human whole blood in the presence of PDTC (60 μM). PDTC significantly inhibited the production of nitrite, IL-1β and IL-6 in these cells. TNFα release was stimulated in murine cells, but suppressed in human whole blood. We further investigated the influence of PDTC on mortality and cytokine release in mouse endotoxin shock. PDTC was i.p. injected 30 min prior to the induction of endotoxin shock in female NMRI-mice and survival was significantly improved as compared to controls (48% vs 20%,
n=25 per group). Plasma concentrations of TNFα were slightly augmented while IL-6 levels were decreased in PDTC-treated animals as compared to controls, however, without reaching significance.
We conclude that PDTC is a potent immunomodulatory substance that modulates the inflammatory response in vitro and reduces mortality in mouse endotoxin shock. The pathophysiological mechanisms of the protective effect of PDTC in vivo, however, appears to be pluripotent, comprising both antioxidative properties and the inhibition of NF-kB.</abstract><cop>Oxford</cop><pub>Elsevier Science</pub><pmid>10684991</pmid><doi>10.1016/S0192-0561(99)00071-5</doi><tpages>8</tpages></addata></record> |
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| subjects | Animals Antioxidant Antioxidants - pharmacology Biological and medical sciences Cell Line Cytokines Cytokines - biosynthesis Female General and cellular metabolism. Vitamins Humans Immunomodulation Immunomodulators Macrophages - drug effects Macrophages - immunology Medical sciences Mice Mouse endotoxin shock NF-kappa B Nitric Oxide - biosynthesis PDTC Pharmacology. Drug treatments Pyrrolidine dithiocarbamate Pyrrolidines - pharmacology Shock, Septic - drug therapy Thiocarbamates - pharmacology Thiocarbamates - toxicity |
| title | Influence of pyrrolidine dithiocarbamate on the inflammatory response in macrophages and mouse endotoxin shock |
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