Abstract | OBJECTIVE: DESIGN: A prospective, randomized in vivo animal laboratory study. SETTING: Experimental research laboratory. INTERVENTION: We performed experiments in which CpG, LPS and D-GalN were administrated sequentially in various orders or simultaneously in 8 week-old BALB/c mice. MEASUREMENTS AND RESULTS:
Cytosine- phosphate- guanine treatment potentiated LPS action only if injected prior to LPS. A combination of predefined sublethal doses of CpG (1 nmol/mouse) and LPS (1 ng/mouse) not only had a synergetic effect on TNF-alpha production (20.3+/-9.2 IU/ml versus 2.5+/-1.4 IU/ml and 5.6+/-3.4 IU/ml for CpG and LPS groups, respectively, p<0.05), but also led to animal death (5/5). An CpG effect requires de novo mRNA synthesis, since the sensitizing effect was inhibited by co-administration of mRNA transcription inhibitors such as D-GalN and pentoxifylline, which is a specific TNF-alpha transcription inhibitor. Furthermore, CpG treatment provoked a strong TNF-alpha mRNA production in the liver that was dramatically reduced by pre-treatment with D-GalN. CONCLUSION: Our findings indicate that CpG motifs act synergistically with LPS by initializing the synthesis of TNF-alpha and/or TNF-alpha regulating factors, thereby acting as a sensitizing agent.
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Authors | Sylvie Cornélie, Eric Wiel, Niels Lund, Gilles Lebuffe, Catherine Vendeville, Gilles Riveau, Benoît Vallet, Elisabeth Ban |
Journal | Intensive care medicine
(Intensive Care Med)
Vol. 28
Issue 9
Pg. 1340-7
(Sep 2002)
ISSN: 0342-4642 [Print] United States |
PMID | 12209287
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA Primers
- Lipopolysaccharides
- RNA, Messenger
- Thionucleotides
- Tumor Necrosis Factor-alpha
- Pentoxifylline
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Topics |
- Animals
- Base Sequence
- CpG Islands
(physiology)
- DNA Primers
- Lipopolysaccharides
(toxicity)
- Mice
- Mice, Inbred BALB C
- Models, Biological
- Pentoxifylline
(pharmacology)
- Prospective Studies
- RNA, Messenger
(genetics)
- Shock, Septic
(chemically induced, metabolism)
- Thionucleotides
(chemistry)
- Tumor Necrosis Factor-alpha
(biosynthesis, genetics)
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