SODIUM FUSIDATE AND THE CYTOKINE RESPONSE IN AN EXPERIMENTAL-MODEL OFACUTE-PANCREATITIS

Background New therapies designed to downregulate the aberrant immune response associated with severe acute necrotizing pancreatitis (ANP) a re being increasingly investigated in different experimental models of ANP. The aim of this study was to test the potential effects of sodiu m fusidate on the course of severe ANP in rabbits. Methods ANP was ind uced in 20 rabbits by retrograde injection of 5 per cent chenodeoxycho lic acid into the pancreatic duct followed by duct ligation. The rabbi ts were allocated to pretreatment with intravenous physiological salin e or sodium fusidate 80 mg/kg 30 min before the induction of ANP. Leve ls of serum amylase, lipase, tumour necrosis factor (TNF) alpha, inter leukin (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 f luid was collected and the pancreatic, lung and kidney tissues were ob tained for histological examination. Results Pretreatment 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 < 0.001). Serum levels of TNF-alpha and IL-8 were reduced significa ntly 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 sign ificantly improved in the group treated with sodium fusidate (P = 0.05 5). By contrast, both treated and untreated rabbits had similar bioche mical changes including levels of amylase, lipase, glucose and calcium as well as similar histological changes in the pancreas and lungs. Co nclusion Pretreatment with sodium fusidate resulted in a considerable reduction in mortality rate and ascitic fluid output in rabbits with b ile-induced ANP, probably by lowering the TNF-alpha and IL-8 blood lev els. However, pretreatment with sodium fusidate did not alter the loca l or systemic manifestations of ANP. Thus, cytokines other than TNF-al pha and IL-8 are likely to mediate the local and systemic symptoms of ANP.