Influence of hydroxyethyl starch on lipopolysaccharide-induced tissue nuclear factor kappa B activation and systemic TNF-alpha expression.
BACKGROUND
Several studies have shown beneficial effects of hydroxyethyl starch (HES) on organ damage in the treatment of severe inflammatory situations, but the mechanisms remain unclear. Nuclear factor-kappa B (NF-kappaB) activation is known to contribute to many aspects of inflammatory injury and organ dysfunction in critical illness, and tumor necrosis factor-alpha (TNF-alpha) is considered the most important pro-inflammatory cytokine. The present study was undertaken to test whether HES (200/0.5) has some effects on tissue NF-kappaB activity and systemic TNF-alpha expression induced by lipopolysaccharide in order to define a possible mechanism of the beneficial effects of HES.


METHODS
Male Wistar rats were randomly divided into seven groups treated with saline, lipopolysaccharide (LPS, 6 mg/kg), LPS plus HES (3.75, 7.5, 15, 30 ml/kg), or HES (30 ml/kg) alone. Two hours after LPS challenge, NF-kappaB activation in the lungs, hearts, livers, and kidneys were examined with an electrophoretic mobility shift assay. Four hours after LPS challenge, plasma TNF-alpha concentrations were measured using an enzyme-linked immunosorbance assay.


RESULTS
3.75 and 7.5 ml/kg HES suppressed LPS-induced NF-kappaB activation in the four tissues and decreased plasma TNF-alpha elevation. The effects of 15 ml/kg HES was only significant in inhibiting NF-kappaB activity in the lung and liver. No effect of 30 ml/kg HES was revealed in all the cases.


CONCLUSIONS
Lower doses of HES may inhibit tissue NF-kappaB activation and systemic TNF-alpha elevation after LPS challenge, which might be helpful during sepsis.
Tian
J
J
Department of Anesthesiology, Renji Hospital, Shanghai, China.
Lin
X
X
Li
Y H
YH
Xu
J G
JG
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010952:Plasma Substitutes / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D006895:Hydroxyethyl Starch Derivatives; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins; D010952:Plasma Substitutes; D014409:Tumor Necrosis Factor-alpha; D004247:DNA