SAT0047 Local Cryotherapy Down-Regulates Local and Systemic IL-6 and IL-17 Pathways in Adjuvant-Induced Arthritis

BackgroundCryotherapy is widely and empirically used in an adjuvant and symptomatic setting in inflammatory rheumatic diseases, with a low level of evidence [1].ObjectivesThe aim of this work was to evaluate local and systemic anti-inflammatory effects of local cryotherapy (LC) in adjuvant-induced a...

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Veröffentlicht in:Annals of the rheumatic diseases 2016-06, Vol.75 (Suppl 2), p.680-681
Hauptverfasser: Guillot, X., Martin, H., Maguin-Gaté, K., Py, S., Demougeot, C., Wendling, D., Tordi, N.
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container_end_page 681
container_issue Suppl 2
container_start_page 680
container_title Annals of the rheumatic diseases
container_volume 75
creator Guillot, X.
Martin, H.
Maguin-Gaté, K.
Py, S.
Demougeot, C.
Wendling, D.
Tordi, N.
description BackgroundCryotherapy is widely and empirically used in an adjuvant and symptomatic setting in inflammatory rheumatic diseases, with a low level of evidence [1].ObjectivesThe aim of this work was to evaluate local and systemic anti-inflammatory effects of local cryotherapy (LC) in adjuvant-induced arthritis (AIA), comparing 2 techniques (ice and cold gas spray). We considered clinical (arthritic score and ankle diameter) and biological effects on IL-6, IL-17A, IL-1β, TNF-α local and systemic levels.MethodsArthritis was induced by a single Mycobacterium butyricum injection in male Lewis rat tails (day 0). At the onset of arthritis (day 11), rats were treated either by 30 minute-ice applications on hind paws (in cages lined with ice pops – n=10) or by 2 minute-cold gas pulverizations on both hind paws (n=9) twice a day for 14 consecutive days. Ten non-treated AIA rats were used as controls. At day 24 (the day after the last cold application), hind paws were grinded in order to measure cytokine gene expression levels by Q-RT-PCR. Plasmatic levels of the same cytokines were also measured in plasma by cytometry (Multiplex Magpix® ebioscience). IL-6 plasma levels were measured by ELISA (rat IL6 platinum ELISA, BMS625®, ebioscience).ResultsIce application significantly reduced the mean arthritic score and ankle diameter from day 6 to day 14 (p
doi_str_mv 10.1136/annrheumdis-2016-eular.1779
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We considered clinical (arthritic score and ankle diameter) and biological effects on IL-6, IL-17A, IL-1β, TNF-α local and systemic levels.MethodsArthritis was induced by a single Mycobacterium butyricum injection in male Lewis rat tails (day 0). At the onset of arthritis (day 11), rats were treated either by 30 minute-ice applications on hind paws (in cages lined with ice pops – n=10) or by 2 minute-cold gas pulverizations on both hind paws (n=9) twice a day for 14 consecutive days. Ten non-treated AIA rats were used as controls. At day 24 (the day after the last cold application), hind paws were grinded in order to measure cytokine gene expression levels by Q-RT-PCR. Plasmatic levels of the same cytokines were also measured in plasma by cytometry (Multiplex Magpix® ebioscience). IL-6 plasma levels were measured by ELISA (rat IL6 platinum ELISA, BMS625®, ebioscience).ResultsIce application significantly reduced the mean arthritic score and ankle diameter from day 6 to day 14 (p<0.001) and globally throughout the 14 day treatment period (2-way ANOVA: p<0.001) compared to non-treated AIA controls. Cold gas first aggravated arthritis at days 11–12 (p<0.01) then improved clinical inflammation at days 21–24 (p<0.001). Skin temperature after LC didn't differ between treatment groups. Both techniques significantly reduced IL-6, IL-1β, IL-17A gene expression levels in hind paws at day 24 compared to non-treated AIA (by 60%, 87% and 50% respectively, p<0.001, p<0.001 and p<0.05). Cytokine gene expression levels correlated positively with hind paw arthritic score and ankle diameter. Conversely, LC had no effect on TNF-α gene expression in hind paws. LC also significantly reduced IL-17A plasmatic protein levels at day 24 (Ice: 47±3pg/ml versus 132±15pg/ml; n=9; p<00001 – cold gas: 89±12pg/ml versus 132±15pg/ml; p<0.02) and IL-17A plasmatic levels correlated positively with arthritic score, ankle diameter and negatively with weight gain. Ice also reduced IL-6 plasmatic levels (118±20pg/ml versus 197±60pg/ml; p<0.05). LC had no effect on TNF-α nor IL-1β plasmatic levels.ConclusionsThese results demonstrate in vivo previously unknown therapeutic and anti-inflammatory effects of 14 day-LC in AIA. We observed both local (at the gene level in treated hind paws) and systemic (at the protein level in plasma) down-regulation of key cytokine pathways critically involved in the pathogenesis and severity of inflammatory rheumatic diseases. LC local and systemic anti-inflammatory effects were mainly IL-6/IL-17A-driven and TNF-α-independent in this model.ReferencesGuillot X, et al. Cryotherapy in inflammatory rheumatic diseases: a systematic review. Expert Rev Clin Immunol. 2014;10(2):281–94.Disclosure of InterestNone declared]]></description><identifier>ISSN: 0003-4967</identifier><identifier>EISSN: 1468-2060</identifier><identifier>DOI: 10.1136/annrheumdis-2016-eular.1779</identifier><identifier>CODEN: ARDIAO</identifier><language>eng</language><publisher>Kidlington: Elsevier Limited</publisher><subject>Life Sciences</subject><ispartof>Annals of the rheumatic diseases, 2016-06, Vol.75 (Suppl 2), p.680-681</ispartof><rights>2016, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Copyright: 2016 (c) 2016, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-8459-9465 ; 0000-0002-1217-7351</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://ard.bmj.com/content/75/Suppl_2/680.2.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://ard.bmj.com/content/75/Suppl_2/680.2.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,778,782,883,3185,23554,27907,27908,77351,77382</link.rule.ids><backlink>$$Uhttps://univ-fcomte.hal.science/hal-03547709$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Guillot, X.</creatorcontrib><creatorcontrib>Martin, H.</creatorcontrib><creatorcontrib>Maguin-Gaté, K.</creatorcontrib><creatorcontrib>Py, S.</creatorcontrib><creatorcontrib>Demougeot, C.</creatorcontrib><creatorcontrib>Wendling, D.</creatorcontrib><creatorcontrib>Tordi, N.</creatorcontrib><title>SAT0047 Local Cryotherapy Down-Regulates Local and Systemic IL-6 and IL-17 Pathways in Adjuvant-Induced Arthritis</title><title>Annals of the rheumatic diseases</title><description><![CDATA[BackgroundCryotherapy is widely and empirically used in an adjuvant and symptomatic setting in inflammatory rheumatic diseases, with a low level of evidence [1].ObjectivesThe aim of this work was to evaluate local and systemic anti-inflammatory effects of local cryotherapy (LC) in adjuvant-induced arthritis (AIA), comparing 2 techniques (ice and cold gas spray). We considered clinical (arthritic score and ankle diameter) and biological effects on IL-6, IL-17A, IL-1β, TNF-α local and systemic levels.MethodsArthritis was induced by a single Mycobacterium butyricum injection in male Lewis rat tails (day 0). At the onset of arthritis (day 11), rats were treated either by 30 minute-ice applications on hind paws (in cages lined with ice pops – n=10) or by 2 minute-cold gas pulverizations on both hind paws (n=9) twice a day for 14 consecutive days. Ten non-treated AIA rats were used as controls. At day 24 (the day after the last cold application), hind paws were grinded in order to measure cytokine gene expression levels by Q-RT-PCR. Plasmatic levels of the same cytokines were also measured in plasma by cytometry (Multiplex Magpix® ebioscience). IL-6 plasma levels were measured by ELISA (rat IL6 platinum ELISA, BMS625®, ebioscience).ResultsIce application significantly reduced the mean arthritic score and ankle diameter from day 6 to day 14 (p<0.001) and globally throughout the 14 day treatment period (2-way ANOVA: p<0.001) compared to non-treated AIA controls. Cold gas first aggravated arthritis at days 11–12 (p<0.01) then improved clinical inflammation at days 21–24 (p<0.001). Skin temperature after LC didn't differ between treatment groups. Both techniques significantly reduced IL-6, IL-1β, IL-17A gene expression levels in hind paws at day 24 compared to non-treated AIA (by 60%, 87% and 50% respectively, p<0.001, p<0.001 and p<0.05). Cytokine gene expression levels correlated positively with hind paw arthritic score and ankle diameter. Conversely, LC had no effect on TNF-α gene expression in hind paws. LC also significantly reduced IL-17A plasmatic protein levels at day 24 (Ice: 47±3pg/ml versus 132±15pg/ml; n=9; p<00001 – cold gas: 89±12pg/ml versus 132±15pg/ml; p<0.02) and IL-17A plasmatic levels correlated positively with arthritic score, ankle diameter and negatively with weight gain. Ice also reduced IL-6 plasmatic levels (118±20pg/ml versus 197±60pg/ml; p<0.05). LC had no effect on TNF-α nor IL-1β plasmatic levels.ConclusionsThese results demonstrate in vivo previously unknown therapeutic and anti-inflammatory effects of 14 day-LC in AIA. We observed both local (at the gene level in treated hind paws) and systemic (at the protein level in plasma) down-regulation of key cytokine pathways critically involved in the pathogenesis and severity of inflammatory rheumatic diseases. LC local and systemic anti-inflammatory effects were mainly IL-6/IL-17A-driven and TNF-α-independent in this model.ReferencesGuillot X, et al. Cryotherapy in inflammatory rheumatic diseases: a systematic review. Expert Rev Clin Immunol. 2014;10(2):281–94.Disclosure of InterestNone declared]]></description><subject>Life Sciences</subject><issn>0003-4967</issn><issn>1468-2060</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqVkc1OwzAQhC0EEqXwDpY4cTCsE8dOxCkqP60UCUTL2XISh6Rqk2InrXLjwovyJLgNQlw57e7om9FKg9AlhWtKfX6j6tqUulvnlSUeUE50t1LmmgoRHaERZTx0ModjNAIAn7CIi1N0Zu3SnRDScITsPF4AMPH18Zk0mVrhiembttRGbXp81-xq8qLfXGirLR4AVed43ttWr6sMzxLCD4pbqMDPqi13qre4qnGcL7utqlsyq_Mu0zmOTVuaqq3sOTop1Mrqi585Rq8P94vJlCRPj7NJnJCUcspIKpgAEXGdF5723ZUKP2dFyPw0FNQvIADQ3MsC7jlQhcILvUBEWkCqaOHgMboacku1khtTrZXpZaMqOY0TudfAD5gQEG2pYy8HdmOa907bVi6bztTuPUkjoKEPEDBH3Q5UZhprjS5-YynIfSPyTyNy34g8NCL3jTg3H9zpevkv4ze8w5Ub</recordid><startdate>20160601</startdate><enddate>20160601</enddate><creator>Guillot, X.</creator><creator>Martin, H.</creator><creator>Maguin-Gaté, K.</creator><creator>Py, S.</creator><creator>Demougeot, C.</creator><creator>Wendling, D.</creator><creator>Tordi, N.</creator><general>Elsevier Limited</general><general>BMJ Publishing Group</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</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>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-8459-9465</orcidid><orcidid>https://orcid.org/0000-0002-1217-7351</orcidid></search><sort><creationdate>20160601</creationdate><title>SAT0047 Local Cryotherapy Down-Regulates Local and Systemic IL-6 and IL-17 Pathways in Adjuvant-Induced Arthritis</title><author>Guillot, X. ; Martin, H. ; Maguin-Gaté, K. ; Py, S. ; Demougeot, C. ; Wendling, D. ; Tordi, N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1614-b7470796edf2e3b74b73d4f843b8713f0500e62c562470a87282579e70ba1fb73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Life Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guillot, X.</creatorcontrib><creatorcontrib>Martin, H.</creatorcontrib><creatorcontrib>Maguin-Gaté, K.</creatorcontrib><creatorcontrib>Py, S.</creatorcontrib><creatorcontrib>Demougeot, C.</creatorcontrib><creatorcontrib>Wendling, D.</creatorcontrib><creatorcontrib>Tordi, N.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>BMJ Journals</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>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database (ProQuest)</collection><collection>Biological Science 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 China</collection><collection>ProQuest Central Basic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Annals of the rheumatic diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guillot, X.</au><au>Martin, H.</au><au>Maguin-Gaté, K.</au><au>Py, S.</au><au>Demougeot, C.</au><au>Wendling, D.</au><au>Tordi, N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SAT0047 Local Cryotherapy Down-Regulates Local and Systemic IL-6 and IL-17 Pathways in Adjuvant-Induced Arthritis</atitle><jtitle>Annals of the rheumatic diseases</jtitle><date>2016-06-01</date><risdate>2016</risdate><volume>75</volume><issue>Suppl 2</issue><spage>680</spage><epage>681</epage><pages>680-681</pages><issn>0003-4967</issn><eissn>1468-2060</eissn><coden>ARDIAO</coden><abstract><![CDATA[BackgroundCryotherapy is widely and empirically used in an adjuvant and symptomatic setting in inflammatory rheumatic diseases, with a low level of evidence [1].ObjectivesThe aim of this work was to evaluate local and systemic anti-inflammatory effects of local cryotherapy (LC) in adjuvant-induced arthritis (AIA), comparing 2 techniques (ice and cold gas spray). We considered clinical (arthritic score and ankle diameter) and biological effects on IL-6, IL-17A, IL-1β, TNF-α local and systemic levels.MethodsArthritis was induced by a single Mycobacterium butyricum injection in male Lewis rat tails (day 0). At the onset of arthritis (day 11), rats were treated either by 30 minute-ice applications on hind paws (in cages lined with ice pops – n=10) or by 2 minute-cold gas pulverizations on both hind paws (n=9) twice a day for 14 consecutive days. Ten non-treated AIA rats were used as controls. At day 24 (the day after the last cold application), hind paws were grinded in order to measure cytokine gene expression levels by Q-RT-PCR. Plasmatic levels of the same cytokines were also measured in plasma by cytometry (Multiplex Magpix® ebioscience). IL-6 plasma levels were measured by ELISA (rat IL6 platinum ELISA, BMS625®, ebioscience).ResultsIce application significantly reduced the mean arthritic score and ankle diameter from day 6 to day 14 (p<0.001) and globally throughout the 14 day treatment period (2-way ANOVA: p<0.001) compared to non-treated AIA controls. Cold gas first aggravated arthritis at days 11–12 (p<0.01) then improved clinical inflammation at days 21–24 (p<0.001). Skin temperature after LC didn't differ between treatment groups. Both techniques significantly reduced IL-6, IL-1β, IL-17A gene expression levels in hind paws at day 24 compared to non-treated AIA (by 60%, 87% and 50% respectively, p<0.001, p<0.001 and p<0.05). Cytokine gene expression levels correlated positively with hind paw arthritic score and ankle diameter. Conversely, LC had no effect on TNF-α gene expression in hind paws. LC also significantly reduced IL-17A plasmatic protein levels at day 24 (Ice: 47±3pg/ml versus 132±15pg/ml; n=9; p<00001 – cold gas: 89±12pg/ml versus 132±15pg/ml; p<0.02) and IL-17A plasmatic levels correlated positively with arthritic score, ankle diameter and negatively with weight gain. Ice also reduced IL-6 plasmatic levels (118±20pg/ml versus 197±60pg/ml; p<0.05). LC had no effect on TNF-α nor IL-1β plasmatic levels.ConclusionsThese results demonstrate in vivo previously unknown therapeutic and anti-inflammatory effects of 14 day-LC in AIA. We observed both local (at the gene level in treated hind paws) and systemic (at the protein level in plasma) down-regulation of key cytokine pathways critically involved in the pathogenesis and severity of inflammatory rheumatic diseases. LC local and systemic anti-inflammatory effects were mainly IL-6/IL-17A-driven and TNF-α-independent in this model.ReferencesGuillot X, et al. Cryotherapy in inflammatory rheumatic diseases: a systematic review. Expert Rev Clin Immunol. 2014;10(2):281–94.Disclosure of InterestNone declared]]></abstract><cop>Kidlington</cop><pub>Elsevier Limited</pub><doi>10.1136/annrheumdis-2016-eular.1779</doi><tpages>2</tpages><orcidid>https://orcid.org/0000-0002-8459-9465</orcidid><orcidid>https://orcid.org/0000-0002-1217-7351</orcidid></addata></record>
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title SAT0047 Local Cryotherapy Down-Regulates Local and Systemic IL-6 and IL-17 Pathways in Adjuvant-Induced Arthritis
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