Severe and necrotizing AP characterized by depletion of circulating lymphocytes

Mortality of patients with severe acute pancreatitis (SAP) approaches 30%-40%. An imbalance between the early systemic inflammatory response syndrome (SIRS), and the later compensatory counter-inflammatory response, and development of multiple organ failure (MOF) are considered to be the primary causes of morbidity and mortality in SAP. Excessive leukocyte activation (including neutrophils and monocyte-macrophage lineage) with cytokinemia play a critical role in the pathogenesis of pancreatitis and even more so, of the subsequent inflammatory response. It has been hypothesized that fatal pancreatitis is a consequence of abnormal phagocytic leukocyte hyperstimulation due to deregulation in T- and B-lymphocyte activation. However, the role of lymphocyte activation and its relation to the severity of disease in humans is still poorly understood. Another important drawback is that the majority of information about the alterations of the immune system during the AP comes from in vitro and in vivo studies, and therefore is not always directly applicable and relevant to the clinical situation in human AP.

A research article to be published on April 21, 2010 in the World Journal of Gastroenterology addresses this question. The research team led by Dambrauskas from Department of Surgery, Kaunas University of Medicine, confirmed that human severe and necrotizing AP is characterized by the significant depletion of circulating lymphocytes.

The study demonstrates that serum interleukin (IL)-6 and macrophage migration inhibitory factor (MIF) concentrations are the best discriminators of severe and necrotiz-ing AP as well as possible fatal outcome during the early course of the disease. These cytokines could also be used as early predictors of local (pancreatic necrosis) and systemic complications (SIRS, MOF) later in the course of the disease. Deregulation of the cellular immune system is a key event leading to the development of severe and necrotizing AP. Infiltration of peripheral organs by aberrantly activated inflammatory cells leads to the development of MOF.

Source: World Journal of Gastroenterology