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We thank Dr Fujita for his interest in our work and his comments. The strain of LPS used in this study (LPS from E coli 026:B6) has previously been shown to induce lesions in the liver resembling alcoholic hepatitis1Bhagwandeen B.S. Apte M. Manwarring L. et al.Endotoxin induced hepatic necrosis in rats on an alcohol diet.J Pathol. 1987; 152: 47-53Crossref PubMed Scopus (146) Google Scholar and alcoholic pancreatitis.2Fortunato F. Deng X. Gates L.K. et al.Pancreatic response to endotoxin after chronic alcohol exposure: switch from apoptosis to necrosis?.Am J Physiol Gastrointest Liver Physiol. 2006; 290: G232-G241Crossref PubMed Scopus (83) Google Scholar These studies informed our selection of the dose used in our paper. At a dose of 3 mg/kg, LPS did not induce any significant pancreatic, lung, or liver injury in rats fed the nonalcohol diet in our study, making a systemic inflammatory response unlikely. With regard to the issue of calibration of endotoxin, the LPS used in our study was tested by the supplier SIGMA against an international standard and established to be at a concentration of 500,000 EU/mg. Our experiments were performed with LPS from a single lot, thereby minimizing any variability in terms of LPS activity. Dr Fujita states that the grade of endotoxemia does not necessarily correlate with the severity of acute pancreatitis. Although we acknowledge that the literature in this area is limited, we would like to note that Ammori et al3Ammori B.J. Leeder P.C. King R.F. et al.Early increase in intestinal permeability in patients with severe acute pancreatitis: correlation with endotoxemia, organ failure, and mortality.J Gastrointest Surg. 1999; 3: 252-262Crossref PubMed Scopus (267) Google Scholar have reported, in a series of 85 patients with acute pancreatitis, that intestinal permeability and the grade of endotoxemia do correlate with pancreatitis severity. Experimentally, this concept is supported by the findings of Fortunato et al,2Fortunato F. Deng X. Gates L.K. et al.Pancreatic response to endotoxin after chronic alcohol exposure: switch from apoptosis to necrosis?.Am J Physiol Gastrointest Liver Physiol. 2006; 290: G232-G241Crossref PubMed Scopus (83) Google Scholar who have reported increasing pancreatic lesions with increasing doses of LPS in rats. Although the issue of endotoxin levels and severity of pancreatitis is of interest, the primary aim of our study was to investigate the role of endotoxin as a trigger factor for overt alcoholic pancreatitis. We have provided evidence to support this notion and have developed a clinically relevant animal model of alcoholic pancreatitis that will enable characterization of the chronologic events in alcohol-related pancreatic disease. Endotoxin as a Trigger of Alcoholic PancreatitisGastroenterologyVol. 134Issue 2PreviewI read with interest the study by Dr Vonlaufen et al1 in the October 2007 issue of Gastroenterology. The authors are to be congratulated on making a novel animal model of alcohol-induced pancreatic injury, by which we may be able to elucidate the chronologic sequence of molecular events in the pathogenesis of alcoholic pancreatitis. In a group of alcohol-fed rats, a single intravenous injection of endotoxin at a dose of 3 mg/kg induced histologic findings compatible with the diagnosis of acute pancreatitis. Full-Text PDF