Effects of hydroxyethyl starch on hepatic production of cytokines and activation of transcription factors in lipopolysaccharide-administered rats.
BACKGROUND
Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. Some studies have indicated that HES may have anti-inflammatory effects. The present in vivo study was performed to investigate the effects of HES on hepatic production of cytokines and activation of transcription factors in sepsis.


METHODS
Adult male Sprague-Dawley rats were randomly divided into four groups: rats challenged with lipopolysaccharide (LPS) (5 mg kg(-1)) and treated with saline (64 ml kg(-1)); challenged with LPS (5 mg kg(-1)) and treated with HES (16 ml kg(-1)); injected with saline and treated with HES (16 ml kg(-1)); and saline control. Each hepatic tissue was collected in groups of rats 2 h after induction of endotoxemia for determination of tumour necrosis factor (TNF)-alpha levels, TNF-alpha mRNA expressions, and nuclear factor (NF)-kappaB, activator protein (AP)-1 activities or 3 h after LPS challenge for IL-1beta, IL-6, IL-8, IL-10 levels and the mRNA expressions.


RESULTS
Endotoxemia was associated with significant increases in hepatic proinflammatory cytokine productions and transcription factor activities. HES significantly reduced the increased hepatic levels of TNF-alpha, IL-1beta, IL-6, IL-8 and the mRNAs in the endotoxemic rats. Similarly, HES could inhibit hepatic NF-kappaB and AP-1 activations.


CONCLUSIONS
The results suggest that in sepsis HES may down-regulate hepatic inflammatory mediators production and these anti-inflammatory effects may act through inhibition of NF-kappaB and AP-1 activations.
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Nanjing University School of Medicine, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210 002, China.
Zhou
W
W
Zhang
L D
LD
Xu
J G
JG
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006439:Hemodynamics / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D015289:Leukotrienes / Q000032:analysis / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis; D010952:Plasma Substitutes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
D016207:Cytokines; D018076:DNA, Complementary; D006895:Hydroxyethyl Starch Derivatives; D015289:Leukotrienes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010952:Plasma Substitutes; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha