Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro
Background Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of preterm neon...
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| Veröffentlicht in: | Pediatric research 2017-08, Vol.82 (2), p.215-225 |
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| creator | Schüller, Simone S Wisgrill, Lukas Herndl, Elisabeth Spittler, Andreas Förster-Waldl, Elisabeth Sadeghi, Kambis Kramer, Boris W Berger, Angelika |
| description | Background
Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of preterm neonates
in vitro
compared with monocytes of term infants and adult controls.
Methods
Whole cord blood samples and control adult blood samples were incubated with LPS and PTX. The expression of surface markers, phagocytosis, cytokine secretion, and Toll-like receptor (TLR)4 signaling of monocytes were assessed by flow cytometry. Changes of TLR4-messenger RNA (mRNA) levels were confirmed by reverse-transcriptase PCR.
Results
The expression of CD14, CD11b, CD64, CD71, and CD80 was downregulated by PTX in a dose-dependent manner; the greatest effect was observed on CD14 and CD11b in preterm infants. PTX markedly downregulated LPS-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in all age groups. Early IL-10 production was significantly downregulated by PTX in term and preterm neonates, while remaining unchanged in adults. Moreover, PTX downregulated TLR4 expression of monocytes on cellular and mRNA level, decreased signaling, and suppressed phagocytosis.
Conclusion
PTX downregulated TLR4 expression and signaling, thereby leading to strong anti-inflammatory properties in monocytes. Age-dependent differences were identified for CD14 and CD11b expression and IL-10 production. |
| doi_str_mv | 10.1038/pr.2017.41 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1877525769</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1877525769</sourcerecordid><originalsourceid>FETCH-LOGICAL-c387t-d9c7155b3e2af3981a3f39e9db4f4e1bb6272f7051f70058cb498c0d2e20df883</originalsourceid><addsrcrecordid>eNpl0E2LFDEQBuAgLu64evEHSIMXUXpM5WOSHJfFj4UBF9RzSHdXNEt30ibd4vx7M8wqsntJkdTDW6EIeQF0C5Trd3PeMgpqK-AR2YDktKVCqMdkQymHlhujz8nTUm4pBSG1eELOmWZag4QNsTcYl_Q7-MM4hojNlIZ1dAuWZn_zpQ1xWHscmh-HGXOIfnTT5JaQYhNipTH1hyNNvpkzLpin-u5dXMqx_yssOT0jZ96NBZ_f1Qvy7cP7r1ef2v3nj9dXl_u251ot7WB6BVJ2HJnz3GhwvBY0Qye8QOi6HVPMKyqhHlTqvhNG93RgyOjgteYX5PUpd87p54plsVMoPY6ji5jWYkErJZlUO1Ppq3v0Nq051t9ZMExJqZXZVfXmpPqcSsno7ZzD5PLBArXHtde7Pa7dCqj45V3k2k04_KN_91zB2xMotRW_Y_5v5sO4P1VwjHs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1927558796</pqid></control><display><type>article</type><title>Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>Schüller, Simone S ; Wisgrill, Lukas ; Herndl, Elisabeth ; Spittler, Andreas ; Förster-Waldl, Elisabeth ; Sadeghi, Kambis ; Kramer, Boris W ; Berger, Angelika</creator><creatorcontrib>Schüller, Simone S ; Wisgrill, Lukas ; Herndl, Elisabeth ; Spittler, Andreas ; Förster-Waldl, Elisabeth ; Sadeghi, Kambis ; Kramer, Boris W ; Berger, Angelika</creatorcontrib><description>Background
Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of preterm neonates
in vitro
compared with monocytes of term infants and adult controls.
Methods
Whole cord blood samples and control adult blood samples were incubated with LPS and PTX. The expression of surface markers, phagocytosis, cytokine secretion, and Toll-like receptor (TLR)4 signaling of monocytes were assessed by flow cytometry. Changes of TLR4-messenger RNA (mRNA) levels were confirmed by reverse-transcriptase PCR.
Results
The expression of CD14, CD11b, CD64, CD71, and CD80 was downregulated by PTX in a dose-dependent manner; the greatest effect was observed on CD14 and CD11b in preterm infants. PTX markedly downregulated LPS-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in all age groups. Early IL-10 production was significantly downregulated by PTX in term and preterm neonates, while remaining unchanged in adults. Moreover, PTX downregulated TLR4 expression of monocytes on cellular and mRNA level, decreased signaling, and suppressed phagocytosis.
Conclusion
PTX downregulated TLR4 expression and signaling, thereby leading to strong anti-inflammatory properties in monocytes. Age-dependent differences were identified for CD14 and CD11b expression and IL-10 production.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/pr.2017.41</identifier><identifier>PMID: 28288151</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/92/436/108 ; 692/420/256 ; 692/700/1720/3185 ; 692/700/565/251 ; Adult ; Antigens, CD - metabolism ; Dose-Response Relationship, Drug ; Humans ; In Vitro Techniques ; Infant, Newborn ; Infant, Premature ; Inflammation ; Inflammation - chemically induced ; Inflammation - prevention & control ; Lipopolysaccharides - adverse effects ; Medicine ; Medicine & Public Health ; Monocytes - metabolism ; Neonatal care ; Newborn babies ; Pediatric Surgery ; Pediatrics ; Pentoxifylline - pharmacology ; Phagocytosis - drug effects ; Premature birth ; Sepsis ; translational-investigation</subject><ispartof>Pediatric research, 2017-08, Vol.82 (2), p.215-225</ispartof><rights>International Pediatric Research Foundation, Inc. 2017</rights><rights>Copyright Nature Publishing Group Aug 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-d9c7155b3e2af3981a3f39e9db4f4e1bb6272f7051f70058cb498c0d2e20df883</citedby><cites>FETCH-LOGICAL-c387t-d9c7155b3e2af3981a3f39e9db4f4e1bb6272f7051f70058cb498c0d2e20df883</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28288151$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schüller, Simone S</creatorcontrib><creatorcontrib>Wisgrill, Lukas</creatorcontrib><creatorcontrib>Herndl, Elisabeth</creatorcontrib><creatorcontrib>Spittler, Andreas</creatorcontrib><creatorcontrib>Förster-Waldl, Elisabeth</creatorcontrib><creatorcontrib>Sadeghi, Kambis</creatorcontrib><creatorcontrib>Kramer, Boris W</creatorcontrib><creatorcontrib>Berger, Angelika</creatorcontrib><title>Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background
Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of preterm neonates
in vitro
compared with monocytes of term infants and adult controls.
Methods
Whole cord blood samples and control adult blood samples were incubated with LPS and PTX. The expression of surface markers, phagocytosis, cytokine secretion, and Toll-like receptor (TLR)4 signaling of monocytes were assessed by flow cytometry. Changes of TLR4-messenger RNA (mRNA) levels were confirmed by reverse-transcriptase PCR.
Results
The expression of CD14, CD11b, CD64, CD71, and CD80 was downregulated by PTX in a dose-dependent manner; the greatest effect was observed on CD14 and CD11b in preterm infants. PTX markedly downregulated LPS-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in all age groups. Early IL-10 production was significantly downregulated by PTX in term and preterm neonates, while remaining unchanged in adults. Moreover, PTX downregulated TLR4 expression of monocytes on cellular and mRNA level, decreased signaling, and suppressed phagocytosis.
Conclusion
PTX downregulated TLR4 expression and signaling, thereby leading to strong anti-inflammatory properties in monocytes. Age-dependent differences were identified for CD14 and CD11b expression and IL-10 production.</description><subject>631/92/436/108</subject><subject>692/420/256</subject><subject>692/700/1720/3185</subject><subject>692/700/565/251</subject><subject>Adult</subject><subject>Antigens, CD - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Infant, Newborn</subject><subject>Infant, Premature</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - prevention & control</subject><subject>Lipopolysaccharides - adverse effects</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Monocytes - metabolism</subject><subject>Neonatal care</subject><subject>Newborn babies</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Pentoxifylline - pharmacology</subject><subject>Phagocytosis - drug effects</subject><subject>Premature birth</subject><subject>Sepsis</subject><subject>translational-investigation</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpl0E2LFDEQBuAgLu64evEHSIMXUXpM5WOSHJfFj4UBF9RzSHdXNEt30ibd4vx7M8wqsntJkdTDW6EIeQF0C5Trd3PeMgpqK-AR2YDktKVCqMdkQymHlhujz8nTUm4pBSG1eELOmWZag4QNsTcYl_Q7-MM4hojNlIZ1dAuWZn_zpQ1xWHscmh-HGXOIfnTT5JaQYhNipTH1hyNNvpkzLpin-u5dXMqx_yssOT0jZ96NBZ_f1Qvy7cP7r1ef2v3nj9dXl_u251ot7WB6BVJ2HJnz3GhwvBY0Qye8QOi6HVPMKyqhHlTqvhNG93RgyOjgteYX5PUpd87p54plsVMoPY6ji5jWYkErJZlUO1Ppq3v0Nq051t9ZMExJqZXZVfXmpPqcSsno7ZzD5PLBArXHtde7Pa7dCqj45V3k2k04_KN_91zB2xMotRW_Y_5v5sO4P1VwjHs</recordid><startdate>20170801</startdate><enddate>20170801</enddate><creator>Schüller, Simone S</creator><creator>Wisgrill, Lukas</creator><creator>Herndl, Elisabeth</creator><creator>Spittler, Andreas</creator><creator>Förster-Waldl, Elisabeth</creator><creator>Sadeghi, Kambis</creator><creator>Kramer, Boris W</creator><creator>Berger, Angelika</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20170801</creationdate><title>Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro</title><author>Schüller, Simone S ; Wisgrill, Lukas ; Herndl, Elisabeth ; Spittler, Andreas ; Förster-Waldl, Elisabeth ; Sadeghi, Kambis ; Kramer, Boris W ; Berger, Angelika</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-d9c7155b3e2af3981a3f39e9db4f4e1bb6272f7051f70058cb498c0d2e20df883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/92/436/108</topic><topic>692/420/256</topic><topic>692/700/1720/3185</topic><topic>692/700/565/251</topic><topic>Adult</topic><topic>Antigens, CD - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Infant, Newborn</topic><topic>Infant, Premature</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - prevention & control</topic><topic>Lipopolysaccharides - adverse effects</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Monocytes - metabolism</topic><topic>Neonatal care</topic><topic>Newborn babies</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Pentoxifylline - pharmacology</topic><topic>Phagocytosis - drug effects</topic><topic>Premature birth</topic><topic>Sepsis</topic><topic>translational-investigation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schüller, Simone S</creatorcontrib><creatorcontrib>Wisgrill, Lukas</creatorcontrib><creatorcontrib>Herndl, Elisabeth</creatorcontrib><creatorcontrib>Spittler, Andreas</creatorcontrib><creatorcontrib>Förster-Waldl, Elisabeth</creatorcontrib><creatorcontrib>Sadeghi, Kambis</creatorcontrib><creatorcontrib>Kramer, Boris W</creatorcontrib><creatorcontrib>Berger, Angelika</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schüller, Simone S</au><au>Wisgrill, Lukas</au><au>Herndl, Elisabeth</au><au>Spittler, Andreas</au><au>Förster-Waldl, Elisabeth</au><au>Sadeghi, Kambis</au><au>Kramer, Boris W</au><au>Berger, Angelika</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2017-08-01</date><risdate>2017</risdate><volume>82</volume><issue>2</issue><spage>215</spage><epage>225</epage><pages>215-225</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background
Pentoxifylline (PTX), a methylxanthine derivate with immunomodulating properties, has been used as adjunctive treatment in severe neonatal sepsis. The aim of the study was to investigate the anti-inflammatory effects of PTX on Lipopolysaccharides (LPS)-stimulated monocytes of preterm neonates
in vitro
compared with monocytes of term infants and adult controls.
Methods
Whole cord blood samples and control adult blood samples were incubated with LPS and PTX. The expression of surface markers, phagocytosis, cytokine secretion, and Toll-like receptor (TLR)4 signaling of monocytes were assessed by flow cytometry. Changes of TLR4-messenger RNA (mRNA) levels were confirmed by reverse-transcriptase PCR.
Results
The expression of CD14, CD11b, CD64, CD71, and CD80 was downregulated by PTX in a dose-dependent manner; the greatest effect was observed on CD14 and CD11b in preterm infants. PTX markedly downregulated LPS-induced tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in all age groups. Early IL-10 production was significantly downregulated by PTX in term and preterm neonates, while remaining unchanged in adults. Moreover, PTX downregulated TLR4 expression of monocytes on cellular and mRNA level, decreased signaling, and suppressed phagocytosis.
Conclusion
PTX downregulated TLR4 expression and signaling, thereby leading to strong anti-inflammatory properties in monocytes. Age-dependent differences were identified for CD14 and CD11b expression and IL-10 production.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28288151</pmid><doi>10.1038/pr.2017.41</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | 631/92/436/108 692/420/256 692/700/1720/3185 692/700/565/251 Adult Antigens, CD - metabolism Dose-Response Relationship, Drug Humans In Vitro Techniques Infant, Newborn Infant, Premature Inflammation Inflammation - chemically induced Inflammation - prevention & control Lipopolysaccharides - adverse effects Medicine Medicine & Public Health Monocytes - metabolism Neonatal care Newborn babies Pediatric Surgery Pediatrics Pentoxifylline - pharmacology Phagocytosis - drug effects Premature birth Sepsis translational-investigation |
| title | Pentoxifylline modulates LPS-induced hyperinflammation in monocytes of preterm infants in vitro |
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