Chronic pancreatitis is long-standing inflammation of the pancreas that results in irreversible deterioration of pancreatic structure and function due to organ fibrosis, induration, duct obstruction, atrophy and, consequently, loss of endocrine and exocrine function. Hallmarks of the disease are severe abdominal pain, elevated pancreatic enzyme (amylase, lipase) levels. Chronic pancreatitis is predominantly caused by alcohol abuse, smoking or by other toxic substances and also genetic causes have become more common. In advanced cases the disease may result in pancreatic exocrine insufficiency and/or diabetes. Furthermore, chronic pancreatitis is a well-described risk factor for pancreatic adenocarcinoma, especially in cases of hereditary chronic pancreatitis.
The destruction of acinar cells in the exocrine pancreas leads to infiltration of mononuclear cells, neutrophils and macrophages and to the replacement of the parenchyma by fibrous tissue. It is still not fully understood which process triggers and maintains the inflammatory response underlying chronic pancreatitis.

In various organs, chronic inflammation generates a microenvironment that contains different types of leukocyte, such as normal tissue macrophages, tumor-associated macrophages, dendritic cells, neutrophils, mast cells and T cells. A plethora of cellular mediators, including cytokines, chemokines, and enzymes, complement this microenvironment.

Therefore, we analyzed human pancreatic tissue from patients with chronic pancreatitis and pancreatic cancer to investigate which cytokines and chemokines are playing an important role in inflammatory environment and cancer.

Based on this study we have generated a transgenic mouse model to determine whether the over expression of inflammatory cytokines within the pancreas is sufficient to induce inflammatory infiltrates and, if so, whether that inflammatory infiltrate is a sufficient condition to lead to diabetes and/or cancer. With further intercrossing experiments we also plan to identify which cell types of the immune system are responsible for development of the disease including fibrosis, metaplasia and pancreatic cancer.