Protective roles of hydroxyethyl starch 130/0.4 in intestinal inflammatory response and survival in rats challenged with polymicrobial sepsis

Background: The gut is considered an important target organ of injury after severe insult such as sepsis, trauma and shock. Hydroxyethyl starch (HES) 130/0.4 has been developed to improve the pharmacokinetics of current medium molecular weight HES solutions. We investigated the protective effects of HES 130/0.4 on intestinal inflammatory response and survival in a rat polymicrobial sepsis model induced by cecal ligation and puncture. Methods: Animals were treated with HES 130/0.4 or saline at 4, 10, 16 or 22 h after the induction of sepsis or sham-operation and were sacrificed 2 It after resuscitation. Intestines were harvested for measurement of tumour necrosis factor alpha (TNT-alpha), interleukin (IL)-10 and macrophage inflammatory protein-2 (MIP-2) production by EELISA; intercellular adhesion molecule-1 (ICAM-1) mRNA expression by reverse-transcription PCR; nuclear factor-kappa B (NF-kappa B) by electrophoretic mobility shift assay; neutrophil sequestration by myeloperoxidase (MPO) assay; intestinal permeability by fluorescein isothiocyanate-labeled dextran assay. In addition, the role of HES 130/0.4 in rat survival was observed. Results: Intestinal permeability was significantly decreased after HES 130/0.4 administration in septic rats, which was associated with a reduction in inflammatory mediators and NF-kappa B activation. Furthermore, early administration of HES 130/0.4 after septic insult resulted in greater decrease in inflammatory mediators. In addition, HES 130/0.4 co-administrated with antibiotics not HES 130/0.4 alone greatly improved the survival of septic rats. Conclusions: HES 130/0.4 reduced intestinal permeability by modulating inflammatory response and had a promising effect on survival together with antibiotics under septic conditions. (c) 2006 Elsevier B.V. All rights reserved.