Source:http://linkedlifedata.com/resource/pubmed/id/16398698
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-1-9
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pubmed:abstractText |
The novel immunosuppressant Sanglifehrin A (SFA) is an immunophilin-binding metabolite with a yet unidentified mechanism of action. Several reports demonstrated the effects of SFA on proliferation and cytokine production of purified T cells with in part different results. However, less is known about the impact of SFA on the regulation of innate immune responses. We used a whole blood assay to investigate the impact of SFA on monocyte responses and T-lymphocyte activity/proliferation upon lipopolysaccharide (LPS) stimulation and anti-CD3/anti-CD28 costimulation, respectively. SFA was found to inhibit interleukin (IL)-2 protein expression of T lymphocytes. Whereas IL-2 mRNA expression was significantly reduced after 4 h of costimulation, the mRNA expression of IL-4 and IL-6 but not tumour necrosis factor (TNF)-alpha was inhibited by SFA both after 4 and 24 h of costimulation. The production of IL-2 and IL-6 protein in T lymphocytes was even strongly affected by SFA than the mRNA expression of the respective cytokine. Unlike other immunophilin-binding immunosuppressants, SFA also inhibited LPS-induced IL-6 and TNF-alpha mRNA and protein expression. At the single cell level, SFA was demonstrated to block the intracellular production of IL-6 in CD14+ monocytes but not the expression of other proinflammatory cytokines such as IL-8 and TNF-alpha. On the basis of these data, we propose that SFA may have a significant effect on the initiation and direction of immune responses. Considering the pleiotropic role of bioactive IL-6 production at the interface of innate and acquired immunity in a variety of disease conditions, it was found that these novel aspects of the unique immunosuppressive action could strongly impact on future clinical application of SFA.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Immunophilins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Lactones,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Monokines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Spiro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/sanglifehrin A
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0300-9475
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
63
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
26-34
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:16398698-Cytokines,
pubmed-meshheading:16398698-Humans,
pubmed-meshheading:16398698-Immunophilins,
pubmed-meshheading:16398698-Immunosuppressive Agents,
pubmed-meshheading:16398698-Interleukin-2,
pubmed-meshheading:16398698-Interleukin-6,
pubmed-meshheading:16398698-Kinetics,
pubmed-meshheading:16398698-Lactones,
pubmed-meshheading:16398698-Lipopolysaccharides,
pubmed-meshheading:16398698-Monocytes,
pubmed-meshheading:16398698-Monokines,
pubmed-meshheading:16398698-RNA, Messenger,
pubmed-meshheading:16398698-Spiro Compounds,
pubmed-meshheading:16398698-T-Lymphocytes
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pubmed:year |
2006
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pubmed:articleTitle |
Immunosuppressive activity of the immunophilin-binding drug Sanglifehrin A in human whole blood: potent inhibition of interleukin-6 produced by lymphocytes and monocytes.
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pubmed:affiliation |
Department of Pediatrics, University of Lübeck Medical School, Ratzeburger Allee, Lübeck, Germany. haertel@paedia.ukl.mu-luebeck.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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