Hydroxyethyl starch inhibits NF-kappaB activation and prevents the expression of inflammatory mediators in endotoxic rats.
Hydroxyethyl starch (HES) has been shown to be beneficial in several inflammatory situations, but the mechanisms are unclear. The present study tested the hypothesis that HES has effects on nuclear factor kappa B (NF-kappaB) activation and the expression of inflammatory mediators induced by lipopolysaccharide. Sepsis was induced in male Wistar rats by injection of lipopolysaccharide (LPS, 6 mg/kg, i.p.). At 1 min after the LPS challenge, HES was infused via the right external jugular vein at the following doses: 3.75, 7.5, 15, or 30 ml/kg. NF-kappaB activation in peripheral blood mononuclear cells and neutrophils, plasma concentrations of tumor necrosis factor (TNF)-alpha, cytokine-induced neutrophil chemoattractant (CINC), expression of CD11b on the blood neutrophil cell surface, and neutrophil sequestration in multiple organs were examined 2 or 4 hr after the LPS challenge. Treatment of rats with HES (3.75 and 7.5 ml/kg) prevented LPS-induced NF-kappaB activation, and inhibited, in a dose-related manner, LPS-induced TNF-alpha and CINC expression. The 4 graded doses of HES decreased CD11b expression in a dose-dependent manner. HES significantly reduced neutrophil sequestration in lung, heart, and liver. These results suggest that HES has an anti-inflammatory effect in endotoxic rats. This effect is mediated by inhibition in the production pathways for inflammatory mediators, including NF-kappaB activation.
Tian
Jie
J
School of Life Science, Nanjing University, and Department of Anesthesiology, Jinling Hospital, Nanjing, China.
Lin
Xin
X
Zhou
Wei
W
Xu
Jianguo
J
D000818:Animals; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000097:blood; D019446:Endotoxemia / Q000378:metabolism*; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D039481:CD11b Antigen; D019743:Chemokines, CXC; D006895:Hydroxyethyl Starch Derivatives; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha