Large dose dexamethasone plays important roles in severe acute pancreatitis

Nov 5 2007

Severe acute pancreatitis (SAP) is a fatal systemic disease featuring acute onset, serious conditions, high incidence of complications and 20 - 30% mortality, mainly due to multiple organ failure at its early stage.

The pathogenesis of SAP is closely related to factors such as activation of pancreatin, release of inflammatory mediators, microcirculation disturbance and apoptosis. However, excessive inflammatory mediators release was regarded as a vital role in the development of SAP. In recent years, it has been found that both inflammatory mediators and pancreatic acinar cell apoptosis are participants in the onset of SAP. The apoptosis of pancreatic acinar cells may be a reaction beneficial to the body after the occurrence of SAP.

The effect of glucocorticoid (represented by dexamethasone) on AP/SAP has been an issue in dispute. In 1952, Stephensen for the first time reported the effect of glucocorticoid in AP treatment. Many empirical studies show glucocorticoid can improve the survival of AP animals. Its mechanisms mainly are: inhibiting the generation of inflammatory mediators and/or inhibiting the effects of inflammatory mediators, enhancing body stress, improving microcirculation, alleviating endotoxemia, cleaning free radicals, inhibiting nitric oxide (NO) and expression of NF- kappa B. In terms of administration and dose, many studies also found a large dose of dexamethasone was obviously superior to the small dose dexamethasone in therapeutic effect, and early use of dexamethasone was superior to dexamethasone of the same dose.

The research team, led by Dr. Zhang Xi-Ping from the First People¡¯s Hospital of Hangzhou and 2nd Affiliated Hospital of Zhejiang University, found that the large dose dexamethasone treatment rats¡¯ survival rate, ascites/body weight ratio, plasma amylase and endotoxin content and inflammatory mediators (such as TNF-¦Á and IL-6) were lower than in SAP rats. With the application of tissue microarray technique, it was shown that pathological change of pancreatic tissue and its severity scores were also greatly alleviated with large dose dexamethasone treatment. Compared with the SAP rats, the pancreatic acinar cell apoptosis was induced and the apoptotic index was significantly promoted with the large dose dexamethasone treatment.

The article clarified that large dose dexamethasone therapeutic mechanisms in SAP may be related to the inhibition of inflammatory mediators and the induction of pancreatic acinar cell apoptosis, demonstrated by the application of tissue microarray technique.