Protective effect of Ulinastatin against murine models of sepsis: Inhibition of TNF-α and IL-6 and augmentation of IL-10 and IL-13

Abstract

Excessive production of inflammatory mediators during invasive infection plays a key role in the pathogenesis of sepsis. In an attempt to improve survival of patients with this lethal syndrome, agents were developed to selectively inhibit mediators in this inflammatory response. Ulinastatin (UTI), a human protease inhibitor, inhibits the enhanced production of pro-inflammatory molecules. However, it is unknown if Ulinastatin treatment could result in protective effects for sepsis. The aim of this study was to investigate the role of Ulinastatin on septic rats. Sixty male Wistar rats were divided into six groups, 10 of each: sham-operation plus PBS (5 ml), cecal ligation and puncture (CLP) plus PBS (5 ml), CLP plus UTI (5000 U/kg), CLP plus UTI (10,000 U/kg), CLP plus UTI (20,000 U/kg) and sham-operation plus UTI (10,000 U/kg). Rats in the UTI groups after CLP operation were treated with Ulinastatin by intraperitoneal injection at different doses and then compared with untreated sepsis control animals. The intestinal concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-13 (IL-13) were significantly higher in septic rats than those in normal rats. Ulinastatin administration effectively suppressed the levels of TNF-α and IL-6, whereas it markedly enhanced the levels of IL-10 and IL-13. Ulinastatin may possess a protective role in the septic process by inhibiting TNF-α and IL-6, and augmenting IL-10 and IL-13 concentrations in intestine of septic rats.