The Role of Proinflammatory Cytokines and Adhesion Molecules in Vascular Disorders and Organ Dysfunction in Acute Pancreatitis Patients

Abstract

Introduction. The incidence of acute pancreatitis (AP) in the world has increased over the last years, mainly due to alcohol consumption. The increasing of the AP severity is characterized by pancreatic necrosis, local complications and systemic organ dysfunction and is about 20.0% of all cases of AP. Despite the successes of intensive care, early mortality from AP remains high. The main component in the pathogenesis of acute pancreatitis is the transition from local to the system inflammation that causes the increasing of the disease severity. Changes of microcirculation and endothelial dysfunction are an important step on the way from the mild to severe course of the disease. Aim. To determine the pathogenetic role of proinflammatory cytokines, adrenal molecules and E-selectin in the occurrence of vascular disorders and organ dysfunction in patients with acute necrotic pancreatitis. Materials and methods. The study involved 53 AP patients (28 – severe, 25 – mild). We measured interleukin-6, interleukin-18, ICAM-1 and E-selectin in the blood plasma. Flow in the visceral arteries was assessed with the help of the Doppler sonography. Organ dysfunction was evaluated on the SOFA scale. The severity of pancreatitis in patients was determined according to the criteria of J. H. C. Ranson. Results. Patients with AP during the hospitalization showed an increase of the levels of IL-6 and IL-18 in 12.11 and 2.02 times, respectively. However, a differentiated assessment of the individual forms of AP revealed a significant increase in both proinflammatory cytokines only in the case of acute necrotic pancreatitis, whereas IL-18 was not significantly elevated in patients with edematous pancreatitis. At the same time, the mean values ​​of IL-6 and IL-18 in patients with acute necrotic pancreatitis significantly exceeded the indicators of patients with pulmonary hypertension in 4.25 and 1.84 times, respectively. It has been established that proinflammatory cytokines mediate the damage of organs by their action on the endothelium of blood vessels and leukocytes by the increasing of the expression of adrenal molecules, which in turn leads to rolling, adhesion, aggregation and transmigration of leukocytes in the involved tissues. Cytokines stimulate endothelial cell membrane and cause the increased synthesis of selectin that bind to leukocytes through the appropriate receptors. This leads to roller leukocytes on the walls of postcapillary venules. The activation of intercellular adhesion molecules (ICAM) and vascular cell adhesion molecules (VCAM) on endothelial cells promotes the adhesion of leukocytes to vascular endothelium and their tissue transmigration. Inflammation cells respond to initial events by releasing enzymes and active forms of oxygen that cause damage of the tissues. Conclusions. It was determined that the levels of proinflammatory cytokines and adhesion molecules increase in the blood of AP patients. Their level correlates with the organ dysfunction and disturbances in splanchnic blood flow.

Keywords

• acute pancreatitis
• adhesion molecules
• inflammatory interleukins
• organ dysfunction
• splanchnic blood flow