David J Bentrem1, Raymond J Joehl. 1. Department of Surgery, Northwestern University Feinberg School of Medicine, and Surgical Service, VA Chicago Health Care System, Illinois, USA.
Abstract
OBJECTIVE: The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows. DESIGN: A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed. RESULTS: Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur. CONCLUSIONS: Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.
OBJECTIVE: The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows. DESIGN: A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed. RESULTS: Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur. CONCLUSIONS: Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.
Authors: Aurelia Lugea; Li Nan; Samuel W French; Jorge A Bezerra; Anna S Gukovskaya; Stephen J Pandol Journal: Gastroenterology Date: 2006-09 Impact factor: 22.682
Authors: Robin S Lindsay; Kaitlin Corbin; Ashley Mahne; Bonnie E Levitt; Matthew J Gebert; Eric J Wigton; Brenda J Bradley; Kathryn Haskins; Jordan Jacobelli; Qizhi Tang; Matthew F Krummel; Rachel S Friedman Journal: J Immunol Date: 2014-12-10 Impact factor: 5.422