Mechanism of the effect of hydroxyethyl starch on reducing pulmonary capillary permeability in a rat model of sepsis.

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. Recent studies have indicated that HES may reduce capillary leakage. The present in vivo study was performed to investigate the effects of HES on pulmonary capillary permeability, inflammatory mediators, and transcription factors in sepsis. Septic rats induced by cecal ligation and puncture (CLP) were treated with different doses of HES (7.5, 15, or 30 ml/kg, iv). At 5 or 12 hr after CLPq the rat lung tissues were collected. Pulmonary microvascular permeability, various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6), mRNA expressions (cytokine-induced neutrophil chemoattractant (CINC), P-selectin, CD 11b/CD18 (Mac-1), and intercellular adhesion molecule-1 (ICAM-1)), and activities of nuclear factor (NF)-kappaB and activator protein (AP)-1 were determined in each group. HES, in a dose-related manner, significantly reduced pulmonary capillary permeability in the CLP model of sepsis. HES also down-regulated pulmonary proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) and mRNA expressions (CINC and P-selectin), and inhibited pulmonary activities of NF-kappaB and AP-1. The results suggest that during sepsis HES reduces pulmonary capillary permeability and this beneficial effect of HES may act through down-regulation of inflammatory mediators and suppression of NF-kappaB and AP-1 activation.