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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-11-17
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pubmed:abstractText |
Intestinal inflammation in inflammatory bowel disease (IBD) and experimental models of colitis is characterized by a dysregulated intestinal immune response with elevated levels of Th1 cytokines. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of inflammation in experimental colitis by mechanisms not known. Bacterial DNA contains unmethylated cytosin-guanosin dinucleotides (CpG) which strongly activate Th1-mediated immune responses. To test whether these CpG-motifs modulate intestinal inflammation we treated mice with dextran sulphate sodium (DSS)-induced colitis with CpG-containing oligodeoxynucleotides (CpG-ODN). CpG-ODN given after the onset of DSS colitis aggravated the disease, as indicated by a significantly increased loss of body weight and a 30% increase of the histological score. Further, we found a severe increase of proinflammatory cytokines (interleukin (IL)-6: 40-fold; interferon (IFN)-gamma: 11-fold). In a pretreatment setting CpG-ODN reduced weight loss significantly and reduced intestinal inflammation by 45%. Colonic IFN-gamma and IL-6 mRNA levels were reduced by 75%, and IL-10 was elevated by 400% compared to controls. The prophylactic CpG-effect was not imitated by IL-12 because IL-12 pretreatment was not protective. In time-course experiments, CpG-ODN pretreatment over 5 days resulted in a tolerance effect concerning its IFN-gamma-inducing quality, and during the following days of colitis induction IL-10 secretion from mesenterial lymph node cells was elevated compared to controls. Therefore, the prophylactic effect of CpG-ODN might be explained by its tolerizing effect and/or the increased ability for IL-10 production during the consecutive intestinal inflammation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14616780-10337013,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/14616780-9824576
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0009-9104
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
134
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
217-24
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14616780-Acute Disease,
pubmed-meshheading:14616780-Adjuvants, Immunologic,
pubmed-meshheading:14616780-Animals,
pubmed-meshheading:14616780-Body Weight,
pubmed-meshheading:14616780-Colitis,
pubmed-meshheading:14616780-Colon,
pubmed-meshheading:14616780-CpG Islands,
pubmed-meshheading:14616780-Dextran Sulfate,
pubmed-meshheading:14616780-Disease Models, Animal,
pubmed-meshheading:14616780-Female,
pubmed-meshheading:14616780-Immune Tolerance,
pubmed-meshheading:14616780-Interferon-gamma,
pubmed-meshheading:14616780-Interleukin-12,
pubmed-meshheading:14616780-Interleukin-6,
pubmed-meshheading:14616780-Lymph Nodes,
pubmed-meshheading:14616780-Mesentery,
pubmed-meshheading:14616780-Mice,
pubmed-meshheading:14616780-Mice, Inbred BALB C,
pubmed-meshheading:14616780-Oligodeoxyribonucleotides,
pubmed-meshheading:14616780-Weight Loss
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pubmed:year |
2003
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pubmed:articleTitle |
Contrasting activity of cytosin-guanosin dinucleotide oligonucleotides in mice with experimental colitis.
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pubmed:affiliation |
Department of Internal Medicine I, University of Regensburg, Regensburg, Germany. Florian.Obermeier@klinik.uni-regensburg.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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