The Selective Sirtuin 1 Activator SRT2104 Reduces Endotoxin-Induced Cytokine Release and Coagulation Activation in Humans

Sirtuin 1 influences gene expression and other cellular functions through deacetylation of histone and nonhistone proteins. We here sought to determine the effects of a small molecule sirtuin 1 activator, SRT2104, on inflammation and coagulation induced by lipopolysaccharide in humans. A randomized,...

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Veröffentlicht in:Critical care medicine 2015-06, Vol.43 (6), p.e199-e202
Hauptverfasser: van der Meer, Anne J, Scicluna, Brendon P, Moerland, Perry D, Lin, Jiang, Jacobson, Eric W, Vlasuk, George P, van der Poll, Tom
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Sprache:eng
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Zusammenfassung:Sirtuin 1 influences gene expression and other cellular functions through deacetylation of histone and nonhistone proteins. We here sought to determine the effects of a small molecule sirtuin 1 activator, SRT2104, on inflammation and coagulation induced by lipopolysaccharide in humans. A randomized, double-blind, placebo-controlled study. An academic hospital. Twenty-four healthy humans. All subjects received an intravenous injection with lipopolysaccharide. Subjects were randomized to one of three groups (n=8 per group): 1) pretreatment with oral SRT2104 for 7 days (2 g/d), 2) pretreatment with a single SRT2104 dose (2 g), or 3) placebo. SRT2104 attenuated lipopolysaccharide-induced release of the cytokines interleukin-6 (mean peak levels of 58.8% [p
ISSN:0090-3493
1530-0293
DOI:10.1097/ccm.0000000000000949