Excessive activation of inflammatory mediator cascade during SAP is a major cause of distant organ injury and the high mortality. Cytokines such as TNF- alpha and IL-1 beta are released early in the development of systemic inflammatory response. This leaves a narrow therapeutic window for administration of therapeutics and delayed delivery of that anti-inflammatory therapeutics is not effective after the inflammatory mediator cascade has developed.
A research article to be published on July 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Wang from Centre of Pancreatic Surgery of Xiehe Hospital, Tongji Medical College, Huazhong University of Sciecne and Technology, demonstrated that the serum levels of HMGB1 began to rise significantly at 12 h, and maintained at high levels up to 48 h after induction of experimental SAP in rats. The delayed kinetics indicated that HMGB1 may provide a broader therapeutic window for treating this lethal systemic inflammatory disease. EP was proved could inhibit HMGB1 release from macrophages and prevent the accumulation of serum HMGB1 levels in mice with lethal sepsis through inhibiting NF- kappaB and p38 MAPK signaling. The research, performed by this team, investigated whether delayed EP therapy attenuates experimental SAP via reducing serum HMGB1 levels in rats or not.
In this study, EP significantly reduced serum HMGB1 levels in rats with SAP, even though began delivering EP at 12 h after induction of SAP. It also significantly protected against liver, renal and lung injury, and prolonged survival time of rats. Ethyl pyruvate, a stable lipophilic pyruvate derivatives, is a nontoxic food additive. According to this article, EP may serve potentially as an effective and low-cost therapeutic option against the inflammatory response and MODS in SAP patients.
This report is of interest and considerable potential importance because it indicates that delayed treatment of rats with experimental severe acute pancreatitis with ethyl pyruvate is associated with a reduction of HMGB1 levels in blood; a decrease in lung, kidney, and liver injury; and prolonged survival. The "therapeutic window" for inhibiting this inflammatory mediator appears to be more favorable than for some other mediators which more rapidly reach a peak in the blood.