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Interaction Between Cytokines and Oxidative Stress in Acute Pancreatitis

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Acute pancreatitis is an inflammation initially localized in the pancreatic gland which may lead to local and systemic complications. The development of severe acute pancreatitis is mediated by pathophysiological mechanisms involved in the systemic inflammatory response, cytokines and oxidative stress being their components of major importance. Nevertheless, it is still unknown why an episode of acute pancreatitis remains mild or progresses to a severe form. Activated leukocytes are the main source of cytokines. Interleukin 1β and tumor necrosis factor alpha (TNF-α) initiate and propagate almost all the consequences of the systemic inflammatory response syndrome, leading to amplification of the inflammatory response. It is noteworthy that the systemic inflammatory response is restrained and the rate of mortality decreased in acute pancreatitis when TNF-α is blocked with specific antibodies or in knock-out mice deficient in its receptors. A synergy between pro-inflammatory cytokines and oxidative stress occurs in the development of the inflammatory response in acute pancreatitis. Pro-inflammatory cytokines and oxidative stress trigger common signal transduction pathways that lead to amplification of the inflammatory cascade, mainly through activation of mitogen-activated protein kinases (MAPK) and nuclear factor kappaB (NF-κB). Furthermore, proinflammatory cytokines, particularly TNF-α, and oxidative stress promote each other generating a vicious circle in acute pancreatitis. This cross-talk that arises between pro-inflammatory cytokines and oxidative stress greatly contributes to amplification of the uncontrolled inflammatory cascade through MAPK and NF-κB.

Keywords: Tumor necrosis factor α; glutathione; interleukin 1β; lipid peroxidation; nitric oxide; oxygen free radicals; platelet activating factor; xanthine oxidase

Document Type: Research Article


Affiliations: Department of Physiology, University of Valencia, Avda. Blasco Ibanez 15, 46010 Valencia, Spain.

Publication date: 2006-10-01

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