Source:http://linkedlifedata.com/resource/pubmed/id/11298491
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2001-4-12
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pubmed:abstractText |
Recent studies suggest that increased activation-induced lymphocyte apoptosis (AICD) is detected in mouse splenocytes during polymicrobial sepsis which may contribute to lymphocyte immune dysfunction [i.e., decreased interleukin (IL-)2 and interferon-gamma (IFN-gamma) production] leading to the associated morbidity seen in those animals. Thus, we wanted to examine the hypothesis that immune suppressive agents, such as IL-4, IL-10 or prostaglandin E2(PGE2), known to be elevated in septic animals, also contribute to this increase in AICD. Here we demonstrate that the inclusion of monoclonal antibody (mAb) to IL-10, but not anti-IL-4 or ibuprofen (IBU), blunted this sepsis induced increase in splenocyte AICD. Additionally, septic mice deficient in the IL-10 gene product (-/-) showed neither an increase in AICD nor a loss of IL-2/IFN-gamma release capacity. Interestingly, mAb to IL-10 did not altered the extent of AICD in a Th2-cell line, but exogenous IL-10 did potentiate Th1-like cell line AICD. This was consistent with the finding that the increased AICD seen in septic mouse splenocytes was restricted largely to the CD4+ cells producing IL-2 (Th1-cells) and that mAb to IL-10 treatment suppressed this change. Furthermore, IL-10 appears to mediate its AICD effect by upregulation of the Fas receptor and Fas receptor signaling protein components, but not by altered expression of Bcl/Bax/Bad family members, in septic mouse splenocytes. To the extent that these processes contribute in a pathological fashion to the animal's capacity to survive sepsis we have previously observed that in vivo post-treatment of mice with mAb IL-10 markedly attenuated septic mortality. Collectively, these data indicate that in the septic mouse the Th2 cytokine IL-10 not only serves to actively induce Th1 lymphocyte immune dysfunction but also plays a role in their apoptotic depletion. These processes in turn appear to contribute to the animal's inability to ward off lethal septic challenge.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/Bad protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-Associated Death Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1043-4666
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2001 Academic Press.
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
37-48
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11298491-Animals,
pubmed-meshheading:11298491-Antigens, CD95,
pubmed-meshheading:11298491-Apoptosis,
pubmed-meshheading:11298491-Carrier Proteins,
pubmed-meshheading:11298491-Cells, Cultured,
pubmed-meshheading:11298491-Dinoprostone,
pubmed-meshheading:11298491-Flow Cytometry,
pubmed-meshheading:11298491-Gene Deletion,
pubmed-meshheading:11298491-Interferon-gamma,
pubmed-meshheading:11298491-Interleukin-10,
pubmed-meshheading:11298491-Interleukin-2,
pubmed-meshheading:11298491-Interleukin-4,
pubmed-meshheading:11298491-Lymphocyte Activation,
pubmed-meshheading:11298491-Male,
pubmed-meshheading:11298491-Mice,
pubmed-meshheading:11298491-Proto-Oncogene Proteins,
pubmed-meshheading:11298491-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11298491-RNA, Messenger,
pubmed-meshheading:11298491-Sepsis,
pubmed-meshheading:11298491-Spleen,
pubmed-meshheading:11298491-Th1 Cells,
pubmed-meshheading:11298491-bcl-2-Associated X Protein,
pubmed-meshheading:11298491-bcl-Associated Death Protein
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pubmed:year |
2001
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pubmed:articleTitle |
IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis.
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pubmed:affiliation |
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, RI 02903, USA. AAYALA@LIFESPAN.org
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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