Abstract
New 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. ANP 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) alpha, 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. Pretreatment with sodium fusidate reduced the mortality rate from six of ten to three of ten (P < 005) and reduced the output of ascitic fluid from 5 2 to 2.0 ml/h (P < 0001). Serum levels of TNF-alpha and IL-8 were reduced significantly in the treated group from 5 min up to 9 h after induction of ANP. The leucopenia observed after 3 h in the untreated group was not significantly improved in the group treated with sodium fusidate (P = 0.055). By contrast, both treated and untreated rabbits had similar biochemical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs. Pretreatment 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-alpha 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-alpha and IL-8 are likely to mediate the local and systemic symptoms of ANP.
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