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BACKGROUNDSeveral 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.
METHODSMale 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.
RESULTS3.75 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.
CONCLUSIONSLower doses of HES may inhibit tissue NF-kappaB activation and systemic TNF-alpha elevation after LPS challenge, which might be helpful during sepsis.
NF-kappaB → LPS: " 3.75 and 7.5 ml/kg HES suppressed LPS induced NF-kappaB activation in the four tissues and decreased plasma TNF-alpha elevation "