Omega-3 fatty acid supplementation increases anti-inflammatory cytokines and attenuates systemic disease sequelae in experimental pancreatitis.
BACKGROUND
The cytokines involved in the systemic inflammatory response in acute pancreatitis (AP) comprise lipid mediators (eg, prostanoids, thromboxanes, leukotrienes) generated from arachidonic acid (AA) and eicosapentaenoic acid (EPA). The AA-derived mediators are generated from omega-6-fatty acid (FA) and have strong proinflammatory effects and the EPA-derived mediators generated from omega-3-fatty acid are less active or even exhibit anti-inflammatory effects. Basic parenteral nutrition delivers omega-6-FA and omega-3-FA at a ratio of approximately 7:1.


OBJECTIVE
To investigate whether altering the FA composition by fish oil supplementation (omega-3-FA) affects cytokine production and the parameters reflecting systemic disease severity in experimental AP.


METHODS
Severe AP was induced in 30 rats by standardized intraductal infusion of bile salt and IV cerulein. Six hours after AP induction, rats were randomized to TPN using commercial solutions with identical amounts of glucose, amino acids, and fat but different FA compositions: group 1 received a soybean-based fat solution without additional fish oil and group 2 was supplemented with 0.2 g/kg per day fish oil. TPN was continued for 2 days. Serum concentrations of IL-6 and IL-10 were measured before and after AP induction and at 24 and 48 hours after starting TPN. Routine cardiorespiratory and renal parameters were monitored to assess the systemic response at the organ level.


RESULTS
Animals treated with fish oil had significantly higher IL-10 values (at 24 hours, 63 +/- 7 versus 46 +/- 3 pg/mL), produced more urine (28 +/- 0.9 versus 21 +/- 1.6 mL), and had significantly fewer episodes of respiratory dysfunction (defined as a pO2 < 80 mm Hg or pCO2 > 50 mm Hg for >15 minutes; 29% versus 67%) during the observation period.


CONCLUSIONS
Altering eicosanoid mediator precursor availability by infusion of (omega-3 fatty acid increases anti-inflammatory cytokines in this model of AP. This together with improved renal and respiratory function suggests that the systemic response to pancreatic injury is attenuated.
Foitzik
Thomas
T
Department of Surgery, Benjamin Franklin Medical Center, Freie Universität Berlin, Germany. thomas.foitzik@med.uni-rostock.de
Eibl
Guido
G
Schneider
Paul
P
Wenger
Frank A
FA
Jacobi
Christoph A
CA
Buhr
Heinz J
HJ
D000818:Animals; D016207:Cytokines / Q000097:blood*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D010195:Pancreatitis / Q000139:chemically induced / Q000178:diet therapy*; D010289:Parenteral Nutrition, Total; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013997:Time Factors
D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D018836:Inflammation Mediators