Differential roles of inflammatory cells in pancreatitis

Abstract

The incidence of acute pancreatitis per 100,000 of population ranges from 5 to 80. Patients suffering from hemorrhagic-necrotizing pancreatitis die in 10-24% of cases. 80% of all cases of acute pancreatitis are etiologically linked to gallstone disease immoderate alcohol consumption. As of today no specific causal treatment for acute pancreatitis exists. Elevated C-reactive protein levels above 130,mg/L can also predict a severe course of acute pancreatitis. The essential medical treatment for acute pancreatitis is the correction of hypovolemia. Prophylactic antibiotics should be restricted to patients with necrotizing pancreatitis, infected necrosis or other infectious complications. However, as premature intracellular protease activation is known to be the primary event in acute pancreatitis. Severe acute pancreatitis is characterized by an early inflammatory immune response syndrome (SIRS) and a subsequent compensatory anti-inflammatory response syndrome (CARS) contributing to severity as much as protease activation does. CARS suppresses the immune system and facilitates nosocomial infections including infected pancreatic necrosis, one of the most feared complications of the disease. A number of attempts have been made to suppress the early systemic inflammatory response but even if these mechanisms have been found to be beneficial in animal models they failed in daily clinical practice.

p8 Deficiency Causes Siderosis in Spleens and Lymphocyte Apoptosis in Acute Pancreatitis

“…The course of the disease however is determined by a systemic inflammatory response and a subsequent compensatory anti-inflammatory response syndrome. 5 Although a modified Increased severity of pancreatic lesions was seen in the p8 −/− mice that resolved 96 hours after AP induction. Each row represents an individual mouse.…”

“…1,3,4 Because of the compensatory anti-inflammatory response syndrome, patients are at risk for immunosuppression and predisposed to infection. 5 The spleen has been shown to be importantly involved in the course of AP because the function of spleen lymphocytes is severely impaired during AP and because spleen lymphocytes replenish apoptotic lymphocytes in the circulation. [6][7][8] In contrast, apoptosis in the spleen usually does not occur and has only been reported in a severe disease model in rats using retrograde taurocholate infusion.…”

The ACE2-Angiotensin-(1–7)-Mas Axis Protects Against Pancreatic Cell Damage in Cell Culture

“…This further amplifies the inflammatory reaction and the extent of pancreatic injury. 27 Autodigestion of the pancreas has been observed in experimental animal models treated with cerulein, a cholecystokinin analog. Supramaximal doses of cerulein have resulted in experimental pancreatitis, which is characterized by dysregulation of the production and secretion of digestive enzymes.…”

Republished: Recent advances in autoimmune pancreatitis: type 1 and type 2

“…Future studies will have to address several related issues such as relative roles of B-cells, T-cells and other immune cells52 in the initiation, progression or relapse of AIP. Answering this question is critical for targeting appropriate therapies during the respective phase of the disease and includes the question of whether a Th1 or a Th2 response predominates 38.…”