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Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation
Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these co...
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| Published in: | Scientific reports 2020-03, Vol.10 (1), p.4007, Article 4007 |
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| description | Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion
in vivo
and
in vitro
. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on
in vivo
and
in vitro
IL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes
in vitro
.
In vivo
, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions. |
| doi_str_mv | 10.1038/s41598-020-61006-1 |
| format | article |
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in vivo
and
in vitro
. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on
in vivo
and
in vitro
IL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes
in vitro
.
In vivo
, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-61006-1</identifier><identifier>PMID: 32132609</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13 ; 13/106 ; 13/21 ; 14/63 ; 631/250/256/2516 ; 631/250/371 ; 64 ; 64/60 ; 692/617/375/178 ; 692/699/375/1692 ; Animal models ; Animals ; Anti-inflammatory agents ; Antiepileptic agents ; Anxiety ; Chronic pain ; Concanavalin A ; Cytokines ; Cytokines - immunology ; Disease Models, Animal ; Enzyme-linked immunosorbent assay ; Epilepsy ; Female ; Histology ; Humanities and Social Sciences ; IL-1β ; Immune system ; Immunomodulation ; Inflammation ; Inflammation - chemically induced ; Inflammation - immunology ; Inflammation - pathology ; Interleukin 2 ; Interleukin 6 ; Lipopolysaccharides ; Lipopolysaccharides - toxicity ; Mice ; Mice, Inbred BALB C ; multidisciplinary ; Pregabalin - pharmacology ; Science ; Science (multidisciplinary) ; Spleen ; Spleen - immunology ; Spleen - pathology ; Splenocytes ; Tumor necrosis factor-α</subject><ispartof>Scientific reports, 2020-03, Vol.10 (1), p.4007, Article 4007</ispartof><rights>The Author(s) 2020</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-44b188616c95b890215b50d0dbc14e63b3078c6f2733c7c5184ca8984a5e52fe3</citedby><cites>FETCH-LOGICAL-c540t-44b188616c95b890215b50d0dbc14e63b3078c6f2733c7c5184ca8984a5e52fe3</cites><orcidid>0000-0002-4688-7052</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2371518027/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2371518027?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32132609$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abu-rish, Eman Y.</creatorcontrib><creatorcontrib>Mansour, Ahmad T.</creatorcontrib><creatorcontrib>Mansour, Hebah T.</creatorcontrib><creatorcontrib>Dahabiyeh, Lina A.</creatorcontrib><creatorcontrib>Aleidi, Shereen M.</creatorcontrib><creatorcontrib>Bustanji, Yasser</creatorcontrib><title>Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion
in vivo
and
in vitro
. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on
in vivo
and
in vitro
IL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes
in vitro
.
In vivo
, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.</description><subject>13</subject><subject>13/106</subject><subject>13/21</subject><subject>14/63</subject><subject>631/250/256/2516</subject><subject>631/250/371</subject><subject>64</subject><subject>64/60</subject><subject>692/617/375/178</subject><subject>692/699/375/1692</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anti-inflammatory agents</subject><subject>Antiepileptic agents</subject><subject>Anxiety</subject><subject>Chronic pain</subject><subject>Concanavalin A</subject><subject>Cytokines</subject><subject>Cytokines - immunology</subject><subject>Disease Models, Animal</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epilepsy</subject><subject>Female</subject><subject>Histology</subject><subject>Humanities and Social Sciences</subject><subject>IL-1β</subject><subject>Immune system</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Interleukin 2</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - toxicity</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>multidisciplinary</subject><subject>Pregabalin - pharmacology</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Spleen</subject><subject>Spleen - immunology</subject><subject>Spleen - pathology</subject><subject>Splenocytes</subject><subject>Tumor necrosis factor-α</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp9Uctq3DAUFaWlCdP8QBbF0LUbPW15UwhDmwYG2kWzFrJ8PaPUllxJHphf6ldGM07SZFNtdOC8LhyELgn-TDCTV5ET0cgSU1xWBOOqJG_QOcVclJRR-vYFPkMXMd7j_ARtOGneozNGCaMVbs7R358BtrrVg3WFdTvb2hQzKPZ27wvtugWn4AtzSP63dVBEMAGS9e7E65TAzTpBLOI0ABxj-kGPoz5Jsn1jJz_54RC1MTsdbAdXa--Mdnp_qr0uSuu62UBXjHM4Noy-gyEWvn-V9QG96_UQ4eLxX6G7b19_rb-Xmx83t-vrTWkEx6nkvCVSVqQyjWhlgykRrcAd7lpDOFSsZbiWpuppzZipjSCSGy0bybUAQXtgK_RlyZ3mdoTOgEtBD2oKdtThoLy26jXj7E5t_V7VWAjKqhzw6TEg-D8zxKTu_RxcvllRVpPciHP5CtFFZYKPMUD_3ECwOk6slolVnlidJlYkmz6-vO3Z8jRoFrBFEDPlthD-df8n9gGZ4rYI</recordid><startdate>20200304</startdate><enddate>20200304</enddate><creator>Abu-rish, Eman Y.</creator><creator>Mansour, Ahmad T.</creator><creator>Mansour, Hebah T.</creator><creator>Dahabiyeh, Lina A.</creator><creator>Aleidi, Shereen M.</creator><creator>Bustanji, Yasser</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4688-7052</orcidid></search><sort><creationdate>20200304</creationdate><title>Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation</title><author>Abu-rish, Eman Y. ; Mansour, Ahmad T. ; Mansour, Hebah T. ; Dahabiyeh, Lina A. ; Aleidi, Shereen M. ; Bustanji, Yasser</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-44b188616c95b890215b50d0dbc14e63b3078c6f2733c7c5184ca8984a5e52fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>13</topic><topic>13/106</topic><topic>13/21</topic><topic>14/63</topic><topic>631/250/256/2516</topic><topic>631/250/371</topic><topic>64</topic><topic>64/60</topic><topic>692/617/375/178</topic><topic>692/699/375/1692</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anti-inflammatory agents</topic><topic>Antiepileptic agents</topic><topic>Anxiety</topic><topic>Chronic pain</topic><topic>Concanavalin A</topic><topic>Cytokines</topic><topic>Cytokines - immunology</topic><topic>Disease Models, Animal</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epilepsy</topic><topic>Female</topic><topic>Histology</topic><topic>Humanities and Social Sciences</topic><topic>IL-1β</topic><topic>Immune system</topic><topic>Immunomodulation</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - immunology</topic><topic>Inflammation - pathology</topic><topic>Interleukin 2</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - toxicity</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>multidisciplinary</topic><topic>Pregabalin - pharmacology</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Spleen</topic><topic>Spleen - immunology</topic><topic>Spleen - pathology</topic><topic>Splenocytes</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abu-rish, Eman Y.</creatorcontrib><creatorcontrib>Mansour, Ahmad T.</creatorcontrib><creatorcontrib>Mansour, Hebah T.</creatorcontrib><creatorcontrib>Dahabiyeh, Lina A.</creatorcontrib><creatorcontrib>Aleidi, Shereen M.</creatorcontrib><creatorcontrib>Bustanji, Yasser</creatorcontrib><collection>SpringerOpen</collection><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 & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</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 Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abu-rish, Eman Y.</au><au>Mansour, Ahmad T.</au><au>Mansour, Hebah T.</au><au>Dahabiyeh, Lina A.</au><au>Aleidi, Shereen M.</au><au>Bustanji, Yasser</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2020-03-04</date><risdate>2020</risdate><volume>10</volume><issue>1</issue><spage>4007</spage><pages>4007-</pages><artnum>4007</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion
in vivo
and
in vitro
. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on
in vivo
and
in vitro
IL-1β, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes
in vitro
.
In vivo
, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1β and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32132609</pmid><doi>10.1038/s41598-020-61006-1</doi><orcidid>https://orcid.org/0000-0002-4688-7052</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2020-03, Vol.10 (1), p.4007, Article 4007 |
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| source | Publicly Available Content Database; PubMed Central; Free Full-Text Journals in Chemistry; Springer Nature - nature.com Journals - Fully Open Access |
| subjects | 13 13/106 13/21 14/63 631/250/256/2516 631/250/371 64 64/60 692/617/375/178 692/699/375/1692 Animal models Animals Anti-inflammatory agents Antiepileptic agents Anxiety Chronic pain Concanavalin A Cytokines Cytokines - immunology Disease Models, Animal Enzyme-linked immunosorbent assay Epilepsy Female Histology Humanities and Social Sciences IL-1β Immune system Immunomodulation Inflammation Inflammation - chemically induced Inflammation - immunology Inflammation - pathology Interleukin 2 Interleukin 6 Lipopolysaccharides Lipopolysaccharides - toxicity Mice Mice, Inbred BALB C multidisciplinary Pregabalin - pharmacology Science Science (multidisciplinary) Spleen Spleen - immunology Spleen - pathology Splenocytes Tumor necrosis factor-α |
| title | Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation |
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