Sodium fusidate and the cytokine response in an experimental model of acute pancreatitis

BackgroundNew therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) are being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodium fusidate on the course of severe ANP in rabbits.MethodsANP was induced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycholic acid into the pancreatic duct followed by duct ligation. The rabbits were allocated to pretreatment with intravenous physiological saline or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Levels of serum amylase, lipase, tumour necrosis factor (TNF) α, interleukin (IL) 8, glucose and calcium, and leucocyte count were measured every 3 h for a total of 12 h. At the end of the experiment, ascitic fluid was collected and the pancreatic, lung and kidney tissues were obtained for histological examination.ResultsPretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 0·05) and reduced the output of ascitic fluid from 5·2 to 2·0 ml/h (P ConclusionPretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with bile-induced ANP, probably by lowering the TNF-α and IL-8 blood levels. However, pretreatment with sodium fusidate did not alter the local or systemic manifestations of ANP. Thus, cytokines other than TNF-α and IL-8 are likely to mediate the local and systemic symptoms of ANP.