| Nicotinamide is a potent inhibitor of proinflammatory cytokines. | |
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MedLine Citation:
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PMID: 12519385 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present study investigates the modulating effects of nicotinamide on the cytokine response to endotoxin. In an in vitro model of endotoxaemia, human whole blood was stimulated for two hours with endotoxin at 1 ng/ml, achieving high levels of the proinflammatory cytokines IL-1 beta, IL-6, IL-8 and TNF alpha. When coincubating whole blood, endotoxin and the vitamin B3 derivative nicotinamide, all four cytokines measured were inhibited in a dose dependent manner. Inhibition was observed already at a nicotinamide concentration of 2 mmol/l. At a concentration of 40 mmol/l, the IL-1 beta, IL-6 and TNF alpha responses were reduced by more than 95% and the IL-8 levels reduced by 85%. Endotoxin stimulation activates poly(ADP-ribose)polymerase (PARP), a nuclear DNA repair enzyme. It has been hypothesized that the anti-inflammatory properties of nicotinamide are due to PARP inhibition. In the present study, the endotoxin induced PARP activation was dose dependently decreased with 4-40 mmol/l nicotinamide or 4-100 micro mol/l 6(5H) phenanthridinone, a specific PARP inhibitor. 6(5H)phenanthridinone however, failed to inhibit the proinflammatory cytokines. Thus, the mechanism behind the cytokine inhibition in our model seems not to be due to PARP inhibition. In conclusion, the present study could not only confirm previous reports of a down-regulatory effect on TNFalpha, but demonstrates that nicotinamide is a potent modulator of several proinflammatory cytokines. These findings demonstrate that nicotinamide has a potent immunomodulatory effect in vitro, and may have great potential for treatment of human inflammatory disease. |
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Authors:
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J S Ungerstedt; M Blömback; T Söderström |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Clinical and experimental immunology Volume: 131 ISSN: 0009-9104 ISO Abbreviation: Clin. Exp. Immunol. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2003-01-09 Completed Date: 2003-05-12 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0057202 Medline TA: Clin Exp Immunol Country: England |
Other Details:
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Languages: eng Pagination: 48-52 Citation Subset: IM |
Affiliation:
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Coagulation Research, Department of Surgical Sciences, Karolinska Institutet, Stockholm, Sweden. johanna.ungerstedt@ks.se |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Immunologic
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therapeutic use* Cells, Cultured Cytokines / secretion* Depression, Chemical Dose-Response Relationship, Drug Endotoxemia / drug therapy*, immunology Enzyme Inhibitors / pharmacology Humans Interleukin-1 / secretion Interleukin-6 / secretion Interleukin-8 / secretion Niacinamide / therapeutic use* Phenanthrenes / pharmacology Poly Adenosine Diphosphate Ribose / antagonists & inhibitors Tumor Necrosis Factor-alpha / secretion |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Immunologic; 0/Cytokines; 0/Enzyme Inhibitors; 0/Interleukin-1; 0/Interleukin-6; 0/Interleukin-8; 0/Phenanthrenes; 0/Tumor Necrosis Factor-alpha; 1015-89-0/phenanthridone; 26656-46-2/Poly Adenosine Diphosphate Ribose; 98-92-0/Niacinamide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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