Role of tobacco as compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells

Abstract

s / Pancreatology such as organ failure, necrosis, and mortality. The amount of fluid over the first 24-48 hours needed to be provided. When combining the various studies, the weighted mean of power (sample size) was used to determine the relative value of significance. Sensitivity analysis evaluated sample sizes, timing, type of fluids and severity of patients included. Ten published studies fulfilled the criteria to be included in the analysis, which included 1495 patients. There were 6 retrospective, 4 prospective studies. While 3 studies concluded that aggressive hydration was beneficial, 7 studies showed no benefit and/or harm. Using a weighted mean analysis, when evaluating the effectiveness of aggressive intravenous hydration beyond 24 hours, there was no significant difference in the development of organ failure, pancreatic necrosis or mortality (OR 1.2, CI 0.4 -1.9). However, in a subgroup analysis excluding patients presenting with severe disease, there was a significant benefit to aggressive intravenous hydration in preventing organ failure and/or pancreatic necrosis (OR 1.8, CI 1.5 -2.8, p 1⁄4 0.02). Additionally, there was a significant decrease in organ failure and/or pancreatic necrosis if the aggressive intravenous hydration was given early, within the first 24 hours (OR 2.1, CI 1.6 – 2.9, p1⁄4 0.03) and 6-12 hours (p 1⁄4 0.02). Based on this meta-analysis, aggressive intravenous hydration appears to be most beneficial when applied to patients with acute pancreatitis early in the course of the disease, within the first 6-24 hours, before severe disease develops. In general, there does not appear to be a benefit to aggressive hydration in patients with acute pancreatitis beyond the first 24 hours. Clinicians should recognize the importance of applying the principles of aggressive hydration as early as possible, especially to patients who have mild disease. The benefit of early aggressive hydration appears to be preventing severe disease, organ failure and/or pancreatic necrosis. O-14 Abstract id: 189. Role of tobacco as compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells Maria Luaces-Regueira , Margarita Casti~ neira-Alvari~ no , Julio IglesiasGarcia , Jos e Lari~ no-Noia , J. Enrique Dominguez-Mu~ noz . 1 Foundation for Research In Digestive Diseases, Spain University Hopital of Santiago de Compostela. Foundation for Research in Digestive Diseases, Spain Introduction: Triggering of the inflammatory process through the activation of pro-inflammatory transcription factors, as NFkappaB, and secretion of pro-inflammatory cytokines is a central pathogenic mechanism of chronic pancreatitis (CP). Previous studies suggest a role for alcohol in this inflammatory process, but the effect of tobacco, which is a recognized risk factor for CP, is unknown. Aims: To analyse the effect of tobacco compared with alcohol in the activation of pro-inflammatory factors and cytokine release from pancreatic acinar cells in culture. Materials & methods: Pancreatic acinar cells were isolated from Swiss mouse pancreas by enzymatic (collagenase) and mechanic degradation, filtration and centrifugation. Cells were stimulated over 3 hours with cholecystokinin (CCK, positive control), alcohol (at 10,25,50,75,100 mM) and tobacco (at 0.001,0.01,0.1,0.2,0.4 mg/ml). NFkappaB activation (translocation of the subunit p65 into the nucleus) was measured by Western blot. Interleukin-1b secretionwas analyzed by ELISA in cellular supernatant. Data are shown as mean and standard error, and analyzed by ANOVA test. Results: Tobacco, but not alcohol, induces activation of NFKappaB (2.69þ1.05 fold increase of p65 translocation at 0.1 mg/ml over the negative control). Neither tobacco nor alcohol induces interleukin-1b release, ranging between 14.1 1.1 pg/ml (negative control) to 20.1 3.6 pg/ml (tobacco 0.1 mg/ml), and to 23.8 9.2 pg/ml (ethanol 100 mM) (n.s.). Conclusion: Tobacco, but not alcohol, initiates the inflammatory process through the activation of NFKappaB in acinar cells. By this mechanism, tobacco can act as a pathogenic factor in chronic pancreatitis. O-15 Abstract id: 248. Serotonin mediates pancreatic acinar cell cytoskeletal remodeling in mice Enrica Saponara, Sabrina Sonda, Kamil e Grabliauskaite, Theresia