Background: Leukocyte-endothelium interaction is known to be a remarkable event at the beginning of systemic inflammatory response syndrome. Leukocyte activation and infiltration are believed to be critical steps in the progression from mild to severe pancreatitis and responsible for many of its systemic complications. The aim of this study was to evaluate leukocyte-endothelium interactions in mesenteric postcapillary venules and cytokines serum levels in experimental acute pancreatitis followed by modulation of TNF-alpha production.
Methods: Severe pancreatitis was induced in Wistar rats with a injection of 0.5ml of 2.5% sodium taurocholate into the pancreatic duct. Eighteen rats were divided in 3 groups: Sham (surgical procedure without AP induction), Pancreatitis (AP Induction), and Pentoxifylline (AP induction plus administration of 25 mg/kg pentoxifylline). Intravital microscopy was used to observe inflammatory leukocyte rolling, adhesion, and transendothelial migration in small venules in vivo (venule diameter, 15-25 μm). TNF-alpha, IL-6, and IL-10 levels were measured by ELISA.
Results: Modulation of TNF-alpha by pentoxifylline shows beneficial effects in this experimental model. The Pentoxifylline group had a statistically significant reduction of leukocyte rolling, adhesion, and transendothelial migration in vivo and a statistically significant reduction of inflammatory cytokines levels (IL-6, IL-10, and TNF-alpha).
Conclusion: Modulation of TNF-alpha reduced systemic inflammatory response in this experimental model. Moreover, our data suggest that TNF-alpha induce accumulation (adhesion, and transendothelial migration) of leukocytes in acute pancreatitis.