Hydroxyethyl starch inhibits intestinal production of cytokines and activation of transcription factors in endotoxaemic rats

Abstract

We studied the effect of hydroxyethyl starch (HES) on intestinal production of cytokines and activation of transcription factors in sepsis. Septic rats, induced by intraperitoneal lipopolysaccharide (LPS) (5 mg/kg), were treated with intravenous HES (16 ml/kg) or saline (64 ml/kg). Rat ileal tissues were collected at 2 h, 3 h or 6 h after LPS challenge. Levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6, IL-8 and IL-10, cytokine mRNAs, activities of nuclear factor kappa-B (NF-KB) and activator protein-1 (AP-1), and the number of ileal myeloperoxidase (MPO)-positive cells were determined for each group. HES significantly reduced the LPS-induced increase in intestinal levels of TNF-alpha, IL-1beta, IL-6, IL-8 and their corresponding mRNAs. HES also decreased the number of MPO-positive cells induced by LPS and inhibited activation of NF-kappaB and AP-1. The results suggest that in sepsis, HES may down-regulate intestinal pro-inflammatory cytokine production via suppression of NF-kappaB and AP-1 activation.