Hydroxyethyl starch 130/0.4 inhibits production of plasma proinflammatory cytokines and attenuates nuclear factor-kappaB activation and Toll-like receptors expression in monocytes during sepsis.

BACKGROUND

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes, and could modulate inflammatory response in sepsis. Our aim of this study was to investigate the mechanism of the effect of HES 130/0.4 by studying plasma levels of inflammatory cytokines, nuclear factor-kappaB (NF-kappaB) activation, and Toll-like receptors (TLRs) expression in peripheral monocytes during polymicrobial sepsis.

MATERIALS AND

METHODS

Rats with sepsis induced by cecal ligation and puncture (CLP) were treated with HES130/0.4 (7.5, 15, or 30 mL/kg, intravenously); then, rat plasma and monocytes were isolated from blood 5 h later. The plasma level of cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6), NF-kappaB activity, and mRNA and protein levels of TLRs (TLR2 and TLR4) in peripheral blood monocytes were determined by enzyme-linked immunosorbent assay, electrophoretic mobility shift assay, reverse transcription-polymerase chain reaction, and Western blotting, respectively.

RESULTS

HES130/0.4 dose-dependently reduced the plasma level of TNF-alpha and IL-6 in rats with sepsis. HES130/0.4 also significantly inhibited NF-kappaB activation, and TLRs mRNA and protein levels in peripheral monocytes.

CONCLUSION

During sepsis, HES130/0.4 can down-regulate the inflammatory response, possibly through inhibition of the TLRs/NF-kappaB signaling pathway, and could be one more appropriate plasma substitute in sepsis.