Autocrine and paracrine mechanisms play an important role in pancreatic fibrosis. Pancreatic fibrosis is considered to have multiple etiologies, according to the TIGAR-O theory: Toxic-metabolic, Idiopathic, Genetic, Autoimmune, Recurrent and severe acute pancreatitis, and Obstructive pathways. Recently, new concepts have been proposed: the primary duct hypothesis and the sentinel acute pancreatitis event (SAPE) hypothesis. Both are based on new observations of patients and of the fibrogenic mechanism. Stellate cells are located in the periacinar areas and are stimulated to transform into myofibroblasts. Myofibroblasts are characteristic of smooth muscle cells and multifunctional cells. Myofibroblasts express many cytokines, growth factors (especially fibrogenetic) and also their receptors. Thus, myofibroblasts are key players in autocrine mechanisms. In early acute or chronic pancreatitis, acinar cells and ductular cells suffer cellular damage and then express many cytokines, such as interleukin-1, tumor necrosis factor-alpha, interleukin-6, platelet-derived growth factor, and transforming growth factor-beta. These cytokines recruit inflammatory cells such as neu-trophils, lymphocytes and macrophages, and also stimulate stellate cells to transform into myofibroblasts. Recruited inflammatory cells express further cytokines to continue inflammation and repair. In the intermediate and late stages, there are inflammatory cells, as well as centroacinar cells, ductular cells, and myofibroblasts in the inflammatory sites of the pancreas. Therefore, the cellular interaction between inflammatory cells, epithelial cells, and myofibroblasts drives the chronic inflammatory process of the pancreas. The histopathology of pancreatic fibrosis is classified as interlobular or intralobular fibrosis. Therefore, the characteristic histopathology of pancreatic fibrosis may be based on complicated cellular interaction caused by multiple etiologies with a final common pathway of fibrogenesis in the pancreas.

Copyright © 2007 S. Karger AG, Basel

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