Inflammation and immunosuppression in severe acute pancreatitis

Abstract

Acute pancreatitis (AP) is a common disease, which usually exists in its mild form. However, in a fifth of cases, the disease is severe, with local pancreatic complications or systemic organ dysfunction or both. Because the development of organ failure is the major cause of death in AP, early identification of patients likely to develop organ failure is important. AP is initiated by intracellular activation of pancreatic proenzymes and autodigestion of the pancreas. Destruction of the pancreatic parenchyma first induces an inflammatory reaction locally, but may lead to overwhelming systemic production of inflammatory mediators and early organ failure. Concomitantly, anti-inflammatory cytokines and specific cytokine inhibitors are produced. This anti-inflammatory reaction may overcompensate and inhibit the immune response, rendering the host at risk of systemic infection. At present, there is no specific treatment for AP. Increased understanding of the pathogenesis of systemic inflammation and development of organ dysfunction may provide us with drugs to ameliorate physiological disturbances.

Figure 1

Two-phase hypothesis of development of multiorgan failure. MOF: Multiple organ failure; SIRS: Systemic inflammatory response syndrome; TNF: Tumor necrosis factor; IL: Interleukin; CARS: Compensatory anti-inflammatory response syndrome.