Hydroxyethyl starch 130/0.4 exerts its anti-inflammatory effect in endotoxemic rats by inhibiting the TLR4/NF-kappaB signaling pathway

Abstract

Previous studies demonstrated that hydroxyethyl starch (HES) down-regulates the inflammatory response, but the mechanism is controversial. The present study measured the effects of HES130/0.4 on plasma proinflammatory cytokines levels and the Toll-like receptor-4 (TLR4)/nuclear factor-kappa B (NF-kappaB) signaling pathway in lipopolysaccharide (LPS)-treated rats. Endotoxemia was induced in rats by injection of LPS (5 mg/kg, via tail vein) and the rats were infused with different doses of HES130/0.4 (7.5, 15, or 30 ml/kg, via jugular vein). At 2 hr after the injection of LPS, plasma and peripheral monocytes were collected to determine tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations (enzyme-linked immunosorbent assay), NF-kappaB activities (electrophoretic mobility shift assay), TLR4 mRNA expression (reverse transcription-polymerase chain reaction), and TLR4 protein levels (Western blotting). The infusion of HES130/0.4 in endotoxemic rats, especially 15 ml/kg, significantly reduced the release of plasma TNF-alpha and IL-1beta, which was consistent with the observed inhibitory effects of HES130/0.4 on NF-kappaB activation, TLR4 mRNA expression, and TLR4 protein level in monocytes. Thus, HES130/0.4 evidently exerts its anti-inflammatory effect in endotoxemic rats by inhibiting the TLR4/NF-kappaB signaling pathway, which suggests that HES130/0.4 may useful for treating early Gram-negative sepsis.