Abstracts
2000 Digestive Disease Week

# 2288 Immunonutrition in Acute Experimental Pancreatitis: Omega-3 Fatty Acid Supplementation Increases Anti-Inflammatory Cytokines and Ameliorates Organ Function.
Thomas Foitzik, Guido Eibl, Paul Schneider, F. A. Wenger, C. A. Jakobi, Heinz J. Buhr, Berlin, Germany

Severity of acute pancreatitis (AP) is determined by the extent of pancreatic necrosis and the systemic reaction to pancreatic injury. Pro-inflammatory cytokines (pro-IC), which mediate the systemic response, are arachidonic acid products generated from omega-6 fatty acids (?-6-FA), anti-inflammatory cytokines (anti-IC) are derived from eicosapentaenoic acid generated from omega-3 fatty acids (W-3-FA). Parenteral nutrition delivers ?- 6-FA and W-3-FA at a ratio of approx. 7:1. Altering this fatty acid composition by supplementation of fish oil has been shown to decrease pro-IC and attenuate inflammatory reactions, e.g. in sepsis. This study investigates whether supplementation of ?-3-FA affects cytokine production and clinical parameters reflecting disease severity in experimental AP. Methods: Severe AP was induced in 28 rats by intraductal bile salt infusion and i.v. cerulein. After 6h, severity of AP was assessed by TAP measurement and the increase in hematocrit. Animals were randomized for total parenteral nutrition with identical amounts of glucose (3.6 g/kg/d), amino acids (1.5 g/kg/d) and fat (2 g/kg/d) but different fat compositions: Group 1 received a soybean-based fat solution without (W-6-FA:?-3-FA?7:1), group 2 with fish oil supplementation (W-6-FA:?-3-FA?3:1). Serum concentrations of IL-6 (pro-IC) and IL-10 (anti-IC) and clinical parameters reflecting organ function (heart rate, MAP, arterial blood gases, urine output) were measured at 0,6,12,24 and 48h. Results: All animals developed severe AP as indicated by an increase in hematocrit, TAP and IL-6 without differences between both groups at 6h. At 24 and 48h, IL-6 levels were lower, IL-10 increased. IL-10 values at 24h were higher in fish oil-supplemented animals (63±7 vs 46±3 pg/ml; p<0.05). Animals treated with fish oil produced more urine (28 vs 21 ml; p<0.05) and had fewer episodes of respiratory distress (pO2<80mmHg at 48h in 1/ 12 vs 7/11 rats). Conclusion: Altering the eicosanoid precursor availability by supplementation of ?-3-FA increases the production of anti-IC. This, together with improved renal and respiratory function suggests that the systemic response to pancreatic injury is attenuated. ?-3-FA supplemetation, which is clinically approved, safe an inexpensive, appears to be a logical step towards further improving the outcome in severe AP.