Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice
Objective and design To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods IL-10 KO mice were...
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| Veröffentlicht in: | Inflammation research 2011-03, Vol.60 (3), p.233-243 |
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| creator | Tang-Feldman, Yajarayma J Lochhead, G. Raymond Lochhead, Stephanie R Yu, Cindy Pomeroy, Claire |
| description | Objective and design To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. Results mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Conclusions Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection. |
| doi_str_mv | 10.1007/s00011-010-0259-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3036806</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>902353878</sourcerecordid><originalsourceid>FETCH-LOGICAL-c524t-49d88b858c48cec3e793f10f4813d43c37c44abc2d99374ecd32b129ca7f09473</originalsourceid><addsrcrecordid>eNqFkkuP0zAUhSMEYoaBH8AGLDbAInD9aGNvkFDFo1JHLGAQO8t1bjqeJnawk6L-OP4bTjsMjwWsbOl-5xw_TlE8pPCCAlQvEwBQWgKFEthMleJWcUoFg1KB_HI774HxkksOJ8W9lK4yLZlkd4sTBooxMZufFt-XfsDY4rh1vqRAIvYtDi54ksa-j5gSJtLHUDrftKbrzBDintj9ELIgj4yvSY02opnA1u0wkt4Ml6ENmz355vJuHIhpc4jzG7Jz0bSHEGfNIcZ50o15hgfTDjemDZkaE3l2vjj__HwKRjtgTZar6YBbH-x28uycxfvFnca0CR9cr2fFxds3nxbvy9WHd8vF61VpZ0wMpVC1lGs5k1ZIi5ZjpXhDoRGS8lpwyysrhFlbVivFK4G25mxNmbKmakCJip8Vr46-_bjusLboh3wP3UfXmbjXwTj958S7S70JO82BzyXMs8HTa4MYvo6YBt25ZLFtjccwJq3yT824rOR_STmjohJKQiaf_EVehTH6_A4ZgoqxOagM0SNkY0gpYnNzaAp6KpE-lkjnEumpRFpkzaPfb3uj-NmaDLAjkPrpVzH-Sv6X6-OjqDFBm010SV98ZEA5UCWyRvEfTAzgPA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>850722609</pqid></control><display><type>article</type><title>Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice</title><source>MEDLINE</source><source>SpringerNature Complete Journals</source><creator>Tang-Feldman, Yajarayma J ; Lochhead, G. Raymond ; Lochhead, Stephanie R ; Yu, Cindy ; Pomeroy, Claire</creator><creatorcontrib>Tang-Feldman, Yajarayma J ; Lochhead, G. Raymond ; Lochhead, Stephanie R ; Yu, Cindy ; Pomeroy, Claire</creatorcontrib><description>Objective and design To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. Results mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Conclusions Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.</description><identifier>ISSN: 1023-3830</identifier><identifier>EISSN: 1420-908X</identifier><identifier>DOI: 10.1007/s00011-010-0259-4</identifier><identifier>PMID: 20922456</identifier><language>eng</language><publisher>Basel: Basel : SP Birkhäuser Verlag Basel</publisher><subject>Allergology ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Chemokines - genetics ; Chemokines - immunology ; Cytokines - genetics ; Cytokines - immunology ; Cytomegalovirus ; Cytomegalovirus Infections - immunology ; Cytomegalovirus Infections - pathology ; Dermatology ; Female ; IL-10 ; IL-10 deficient ; Immunology ; Inflammation - immunology ; Inflammation - pathology ; Interleukin-10 - genetics ; Interleukin-10 - immunology ; Liver - pathology ; Liver - virology ; MCMV ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Murine cytomegalovirus ; Muromegalovirus - physiology ; Neurology ; Original Research Paper ; Pharmacology/Toxicology ; Pro-inflammatory cytokines ; repletion ; Rheumatology ; Spleen - pathology ; Spleen - virology ; Viral Load ; Virus Replication</subject><ispartof>Inflammation research, 2011-03, Vol.60 (3), p.233-243</ispartof><rights>The Author(s) 2010</rights><rights>Springer Basel AG 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-49d88b858c48cec3e793f10f4813d43c37c44abc2d99374ecd32b129ca7f09473</citedby><cites>FETCH-LOGICAL-c524t-49d88b858c48cec3e793f10f4813d43c37c44abc2d99374ecd32b129ca7f09473</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00011-010-0259-4$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00011-010-0259-4$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20922456$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang-Feldman, Yajarayma J</creatorcontrib><creatorcontrib>Lochhead, G. Raymond</creatorcontrib><creatorcontrib>Lochhead, Stephanie R</creatorcontrib><creatorcontrib>Yu, Cindy</creatorcontrib><creatorcontrib>Pomeroy, Claire</creatorcontrib><title>Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice</title><title>Inflammation research</title><addtitle>Inflamm. Res</addtitle><addtitle>Inflamm Res</addtitle><description>Objective and design To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. Results mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Conclusions Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.</description><subject>Allergology</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Chemokines - genetics</subject><subject>Chemokines - immunology</subject><subject>Cytokines - genetics</subject><subject>Cytokines - immunology</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus Infections - immunology</subject><subject>Cytomegalovirus Infections - pathology</subject><subject>Dermatology</subject><subject>Female</subject><subject>IL-10</subject><subject>IL-10 deficient</subject><subject>Immunology</subject><subject>Inflammation - immunology</subject><subject>Inflammation - pathology</subject><subject>Interleukin-10 - genetics</subject><subject>Interleukin-10 - immunology</subject><subject>Liver - pathology</subject><subject>Liver - virology</subject><subject>MCMV</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Murine cytomegalovirus</subject><subject>Muromegalovirus - physiology</subject><subject>Neurology</subject><subject>Original Research Paper</subject><subject>Pharmacology/Toxicology</subject><subject>Pro-inflammatory cytokines</subject><subject>repletion</subject><subject>Rheumatology</subject><subject>Spleen - pathology</subject><subject>Spleen - virology</subject><subject>Viral Load</subject><subject>Virus Replication</subject><issn>1023-3830</issn><issn>1420-908X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkkuP0zAUhSMEYoaBH8AGLDbAInD9aGNvkFDFo1JHLGAQO8t1bjqeJnawk6L-OP4bTjsMjwWsbOl-5xw_TlE8pPCCAlQvEwBQWgKFEthMleJWcUoFg1KB_HI774HxkksOJ8W9lK4yLZlkd4sTBooxMZufFt-XfsDY4rh1vqRAIvYtDi54ksa-j5gSJtLHUDrftKbrzBDintj9ELIgj4yvSY02opnA1u0wkt4Ml6ENmz355vJuHIhpc4jzG7Jz0bSHEGfNIcZ50o15hgfTDjemDZkaE3l2vjj__HwKRjtgTZar6YBbH-x28uycxfvFnca0CR9cr2fFxds3nxbvy9WHd8vF61VpZ0wMpVC1lGs5k1ZIi5ZjpXhDoRGS8lpwyysrhFlbVivFK4G25mxNmbKmakCJip8Vr46-_bjusLboh3wP3UfXmbjXwTj958S7S70JO82BzyXMs8HTa4MYvo6YBt25ZLFtjccwJq3yT824rOR_STmjohJKQiaf_EVehTH6_A4ZgoqxOagM0SNkY0gpYnNzaAp6KpE-lkjnEumpRFpkzaPfb3uj-NmaDLAjkPrpVzH-Sv6X6-OjqDFBm010SV98ZEA5UCWyRvEfTAzgPA</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Tang-Feldman, Yajarayma J</creator><creator>Lochhead, G. Raymond</creator><creator>Lochhead, Stephanie R</creator><creator>Yu, Cindy</creator><creator>Pomeroy, Claire</creator><general>Basel : SP Birkhäuser Verlag Basel</general><general>SP Birkhäuser Verlag Basel</general><general>Springer Nature B.V</general><scope>FBQ</scope><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>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110301</creationdate><title>Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice</title><author>Tang-Feldman, Yajarayma J ; Lochhead, G. Raymond ; Lochhead, Stephanie R ; Yu, Cindy ; Pomeroy, Claire</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-49d88b858c48cec3e793f10f4813d43c37c44abc2d99374ecd32b129ca7f09473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Allergology</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Chemokines - genetics</topic><topic>Chemokines - immunology</topic><topic>Cytokines - genetics</topic><topic>Cytokines - immunology</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus Infections - immunology</topic><topic>Cytomegalovirus Infections - pathology</topic><topic>Dermatology</topic><topic>Female</topic><topic>IL-10</topic><topic>IL-10 deficient</topic><topic>Immunology</topic><topic>Inflammation - immunology</topic><topic>Inflammation - pathology</topic><topic>Interleukin-10 - genetics</topic><topic>Interleukin-10 - immunology</topic><topic>Liver - pathology</topic><topic>Liver - virology</topic><topic>MCMV</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Murine cytomegalovirus</topic><topic>Muromegalovirus - physiology</topic><topic>Neurology</topic><topic>Original Research Paper</topic><topic>Pharmacology/Toxicology</topic><topic>Pro-inflammatory cytokines</topic><topic>repletion</topic><topic>Rheumatology</topic><topic>Spleen - pathology</topic><topic>Spleen - virology</topic><topic>Viral Load</topic><topic>Virus Replication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang-Feldman, Yajarayma J</creatorcontrib><creatorcontrib>Lochhead, G. 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Raymond</au><au>Lochhead, Stephanie R</au><au>Yu, Cindy</au><au>Pomeroy, Claire</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice</atitle><jtitle>Inflammation research</jtitle><stitle>Inflamm. Res</stitle><addtitle>Inflamm Res</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>60</volume><issue>3</issue><spage>233</spage><epage>243</epage><pages>233-243</pages><issn>1023-3830</issn><eissn>1420-908X</eissn><abstract>Objective and design To determine the role of interleukin-10 (IL-10) in protecting against the deleterious pro-inflammatory cytokine response to murine cytomegalovirus (MCMV), we studied the impact of IL-10 repletion in MCMV-infected IL-10 knockout (KO) mice. Materials and methods IL-10 KO mice were infected with a sub-lethal dose of MCMV and treated daily with 5 μg of mouse recombinant IL-10 (mrIL-10). Cytokine transcription, viral load, cytokine expression and liver histopathology were assessed in IL-10 treated and untreated mice. Results mrIL-10 repletion suppressed the exaggerated pro-inflammatory cytokine response observed in IL-10 KO mice (vs. control) both systemically and at the organ level, without affecting viral load. Levels of IFN-γ and TNF-α mRNA in livers of treated mice were ~50-70-fold lower than in untreated mice at day 5 post-infection (p ≤ 0.05). In spleens and sera, levels of IFN-γ and IL-6 were significantly lower in treated mice than in untreated mice at day 5-7 post-infection (p ≤ 0.05). IL-10 blunting of cytokine responses was accompanied by attenuation of inflammation in livers of treated mice. Conclusions Repletion of IL-10 modulates the exaggerated pro-inflammatory cytokine responses that characterize IL-10 KO mice and protects against liver damage without altering viral load. IL-10 may be useful to control dysregulated pro-inflammatory cytokines responses during CMV infection.</abstract><cop>Basel</cop><pub>Basel : SP Birkhäuser Verlag Basel</pub><pmid>20922456</pmid><doi>10.1007/s00011-010-0259-4</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Inflammation research, 2011-03, Vol.60 (3), p.233-243 |
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| subjects | Allergology Animals Biomedical and Life Sciences Biomedicine Chemokines - genetics Chemokines - immunology Cytokines - genetics Cytokines - immunology Cytomegalovirus Cytomegalovirus Infections - immunology Cytomegalovirus Infections - pathology Dermatology Female IL-10 IL-10 deficient Immunology Inflammation - immunology Inflammation - pathology Interleukin-10 - genetics Interleukin-10 - immunology Liver - pathology Liver - virology MCMV Mice Mice, Inbred C57BL Mice, Knockout Murine cytomegalovirus Muromegalovirus - physiology Neurology Original Research Paper Pharmacology/Toxicology Pro-inflammatory cytokines repletion Rheumatology Spleen - pathology Spleen - virology Viral Load Virus Replication |
| title | Interleukin-10 repletion suppresses pro-inflammatory cytokines and decreases liver pathology without altering viral replication in murine cytomegalovirus (MCMV)-infected IL-10 knockout mice |
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