Effects of hydroxyethyl starch (130 kD) on brain inflammatory response and outcome during normotensive sepsis.

Abstract

BACKGROUND:

During sepsis, the dysfunction of blood-brain barrier (BBB) was mediated by inflammation and subsequently caused sepsis-associated encephalopathy. Hydroxyethyl starch (HES, 130/0.4) is most widely used for volume replacement to maintain or improve tissue perfusion in patients with sepsis, trauma, and shock. This study was undertaken to investigate the effects of HES on BBB permeability, brain edema, inflammatory response and clinical outcome in septic rats.

METHODS:

Using the cecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with 15 ml/kg HES or normal saline 4h after the operation. Two hours later, expressions of brain toll-like receptor (TLR)-2, TLR4 and intercellular adhesion molecule (ICAM)-1 mRNA was determined by real-time reverse transcription-polymerase chain reaction; inflammatory cytokines like tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 by enzyme-linked immunosorbent assay; activity of nuclear factor-kappa B (NF-kappaB) by electrophoretic mobility shift assay; BBB permeability by Evans blue extravasation method; brain edema by wet/dry weight ratio. Weight loss, and clinical symptoms were also observed.

RESULTS:

Without obvious influence on systemic macrohemodynamics, HES could markedly attenuate BBB dysfunction and brain edema. Meanwhile, HES could significantly reduce TNF-alpha, IL-6, and ICAM-1 mRNA, inhibit NF-kappaB activation, and down-regulate TLR2 and TLR4 expression in the brain. In addition, CLP-induced increase in weight loss, and clinical symptoms was not reduced after treatment with HES.

CONCLUSIONS:

HES could ameliorate BBB dysfunction and inflammation mediators by modulating brain TLR2 and TLR4 expression during sepsis. However, HES could not improve clinical outcome.

• Authors: Xiaomei Feng, Fujun Zhang, Rong Dong, Haibin Wang, Jian Liu, Xuesheng Liu, Weiyan Li, Jingxin Yao, Jianguo Xu, Buwei Yu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 10 Issue 8 Pg. 859-64 (Aug 2010) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 20451670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Hydroxyethyl Starch Derivatives
• Interleukin-6
• NF-kappa B
• Tlr2 protein, rat
• Tlr4 protein, rat
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Blood-Brain Barrier (drug effects, pathology)
• Brain (drug effects, immunology, metabolism, pathology)
• Cells, Cultured
• Disease Models, Animal
• Encephalitis
• Humans
• Hydroxyethyl Starch Derivatives (administration & dosage)
• Intercellular Adhesion Molecule-1 (genetics, immunology, metabolism)
• Interleukin-6 (biosynthesis, genetics, metabolism)
• NF-kappa B (biosynthesis, genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, immunology)
• Toll-Like Receptor 2 (genetics, immunology, metabolism)
• Toll-Like Receptor 4 (genetics, immunology, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)
• Typhlitis (drug therapy, immunology, pathology, physiopathology)