Endotoxemia is always accompanied with systemic inflammatory response syndrome, which induces multiple organ failure, including the lung, liver, and kidney. Microvascular injury and increased vascular endothelial permeability are its characteristic features. One crucial event that leads to this injury is neutrophil activation followed by neutrophil infiltration and accumulation in various organs. Bacterial endotoxin (lipopolysaccharide; LPS) can induce the expression of adhesion molecules (E selectin, P selectin, and intercellular adhesion molecule-1 [ICAM-1]) on endothelial cells; activate and upregulate integrins (CD11b/CD18) on the neutrophil cell surface ^[5]; cause the expression of chemokines, including interleukin (IL)-8 and cytokine-induced neutrophil chemoattractant (CINC) in several constitutive cells and resident macrophages ^[6,7]; and release other proinflammatory cytokines (tumor necrosis factor (TNF)-α and IL-1) ^[8]. These mediators then act in concert to promote neutrophil activation and migration into the interstitium, where neutrophils cause endothelial cell and tissue damage by releasing elastase, cathepsin G, and oxygen free radicals, leading to capillary leak and tissue edema ^[9].<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

Nuclear factor-_kB (NF-_kB) is an important regulation factor that plays an essential role in the transcriptional induction of cell adhesion molecules, chemokines, proinflammatory cytokines, and enzymes that contribute to endothelial damage and development of multiorgan injury ^[10]. NF-_kB can be induced by LPS in many organs and is increased in neutrophils in endotoxemia ^[11].

No studies have investigated the effects of HES on capillary permeability in acute endotoxemia. In this study, we used a third-generation HES with a medium molecular weight and a low degree of substitution (HES 200/0.5) to determine its effect on lung capillary permeability in endotoxic rats, the effects on lung neutrophil accumulation, expression of CD11b on the blood neutrophil cell surface, lung CINC protein level, and NF-_kB activation in blood neutrophils and lungs, exploring the possible mechanisms underlying its reduction in capillary leak.