| Production of TNF alpha by LPS-stimulated murine, rat and human blood and its pharmacological modulation. | |
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MedLine Citation:
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PMID: 8317328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumour necrosis factor alpha (TNF alpha) has been reported to play a key role in the pathogenesis of sepsis and chronic inflammatory diseases, including rheumatoid arthritis and atherosclerosis, suggesting that agents which inhibit TNF alpha production may have therapeutic utility for the treatment of such conditions. Production of TNF alpha by LPS (lipopolysaccharide)-stimulated murine, rat and human heparinized blood was investigated. LPS (1-100 micrograms/ml) caused a similar concentration- and time-dependent stimulation of TNF alpha production by rat and human blood, achieving levels of 750-5000 U/ml (L929 bioassay) at 6 h. In contrast, TNF alpha production by LPS-stimulated murine blood was poor and variable (0-150 U/ml). Dexamethasone and pentoxifylline caused a concentration-dependent inhibition of TNF alpha production by LPS-stimulated human and rat blood with IC50s of 0.26 +/- 0.05 and 73.0 +/- 26.4 microM for human and 5.7 +/- 1.8 nM and 20.6 +/- 8.0 microM for rat blood, respectively. Therefore, LPS-stimulated rat and human, but not murine, blood are suitable systems for the detection and evaluation of inhibitors of TNF alpha production. |
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Authors:
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S J Foster; L M McCormick; B A Ntolosi; D Campbell |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Agents and actions Volume: 38 Spec No ISSN: 0065-4299 ISO Abbreviation: Agents Actions Publication Date: 1993 |
Date Detail:
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Created Date: 1993-07-29 Completed Date: 1993-07-29 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0213341 Medline TA: Agents Actions Country: SWITZERLAND |
Other Details:
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Languages: eng Pagination: C77-9 Citation Subset: IM |
Affiliation:
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ICI Pharmaceuticals, Macclesfield, Cheshire, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Cells / metabolism* Dexamethasone / pharmacology Humans Lipopolysaccharides / pharmacology* Mice Mice, Inbred BALB C Pentoxifylline / pharmacology Rats Tumor Necrosis Factor-alpha / antagonists & inhibitors, biosynthesis* |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 50-02-2/Dexamethasone; 6493-05-6/Pentoxifylline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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