Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-4-12
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1043-4666
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37-48
pubmed:dateRevised
2008-11-21
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
pubmed:year
2001
pubmed:articleTitle
IL-10 mediation of activation-induced TH1 cell apoptosis and lymphoid dysfunction in polymicrobial sepsis.
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
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.