A Priori Dietary Ω-3 Lipid Supplementation Results in Local Pancreatic Macrophage and Pulmonary Inflammatory Response Attenuation in a Model of Experimental Acute Edematous Pancreatitis (AEP)

Background: Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an ω-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both Mϕ-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). Methods: Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (ω-3 fatty acid; 5 mg/kg/dose) or ω-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in ω-3, ω-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). Results: All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower (p < .05) LRB in the ω-3-treated group compared with theω -6 and the saline pancreatitis group. Conclusions: Attenuation of both pancreatic MΦ inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.

Ω-3 fatty acid, an anti-inflammatory agent, was used to attenuate both local pancreatic macrophage infiltration and pulmonary leukocyte respiratory burst in acute pancreatitis. As a pilot study, this findings will lay the groundwork for future evaluation of the cellular mechanisms involved and also may guide dietary therapeutic modulation to limit pancreatitis-associated sequelae.