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Query: UMLS:C0001339 (acute pancreatitis)
 10,593 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple organ failure (MOF) is a critical condition developing in patients with overwhelming bodily injury resulting from major surgical insult, severe trauma, extensive burns, acute pancreatitis, and sepsis. It has recently become evident that the host response to such injury is the main pathogenetic factor contributing to the development of MOF. The proinflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 are known to play a pivotal role in the pathogenetic mechanisms of MOF. In response to bodily injury, macrophages produce and release TNF and IL-1, which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators. The resultant systemic inflammation may develop into MOF mainly through neutrophil-endothelial cell interaction when the primary injury is overwhelming or a second inflammatory insult such as sepsis triggers an exacerbated inflammation. It has recently been confirmed that the transcription factor NF-kappaB is involved in the up-regulation of a variety of proinflammatory genes and that cell-mediated immunity is down-regulated in the event of major bodily injury through a shift in the balance between T helper 1 (Th1) and Th2 cytokine response patterns. The molecular immunological mechanisms by which these factors participate in the development of MOF should be characterized.
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PMID:[Mechanism of the development of organ failure]. 978 82

Excessive leukocyte activation has been proposed as a key mechanism in the onset of acute pancreatitis. In this study, we assessed the systemic release of various inflammatory mediators and tried to identify differences between patients with mild and severe disease. In a prospective study, 19 patients admitted for severe acute pancreatitis were compared with 24 patients with mild pancreatitis. Serum levels of interleukin-6 (IL-6), IL-8, and IL-10 were determined at the time of admission, and on days 1, 2, and 5 after hospitalization. Severity of pancreatitis was determined according to the Atlanta criteria. IL-6 levels peaked on admission in both groups with significant differences (p < 0.05) from days 0-2. IL-8 levels increased from day 0 in severe cases, and from day 1 in mild cases, to reach a plateau between days 2 and 5; significant differences were observed on days 0 and 1. IL-10 was highest on day 0; it decreased rapidly in mild cases but stayed significantly higher from days 1 to 5 in severe cases. These findings provide new evidence on the role of mediators of the inflammatory/antiinflammatory balance in acute pancreatitis. These molecules appear to be valuable early markers of severity.
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PMID:Serum profiles of interleukin-6, interleukin-8, and interleukin-10 in patients with severe and mild acute pancreatitis. 1023 42

During the last few years attention has been focused on an important role of inflammatory mediators in the pathophysiology and systemic complications of acute pancreatitis. The present study deals with those of the mediators which have shown demonstrable activity in the course of pancreatitis, e.g. acute-phase proteins (among others C-reactive protein and alpha-1-antitrypsin) and neutrophil elastase (PMN-elastase) as the marker for granulocyte activity. The activity of cytokines IL-6, IL-8 and IL-1, of alpha-cachectin (TNF alpha), as well as of the platelet-activating factor (PAF) and the trypsinogen activation peptide (TAP), was discussed.
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PMID:[Inflammatory mediators in the acute pancreatitis]. 1033 84

Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.
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PMID:Inflammatory mediators in acute pancreatitis. 1065 8

The molecular mechanisms that link acute pancreatitis and multiple organ failure remain unknown. We examined the effect of ascitic fluids prepared from rats with experimental necrotizing pancreatitis on the expression of interleukin (IL) -6 and IL-8 in human umbilical vein endothelial cells (HUVEC) and human monocytic THP-1 cells. Incubation of HUVEC or THP-1 cells with the ascitic fluids resulted in a concentration-dependent up-regulation of the cytokine expression with comparable mRNA induction. Electrophoretic mobility shift assay revealed that the ascitic fluids increased the nuclear factor-kappaB (NF-kappaB) and NF-IL6 binding activities. Intraperitoneal injection of ascitic fluids into healthy rats induced the activation of NF-kappaB in the infiltrating leukocytes in the lung. Our results suggested that ascitic fluids may play a role in the pathophysiology of severe acute pancreatitis through the activation of transcription factors and consequent cytokine productions in distant organs.
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PMID:Ascites of severe acute pancreatitis in rats transcriptionally up-regulates expression of interleukin-6 and -8 in vascular endothelium and mononuclear leukocytes. 1071 63

We have explored whether lipopolysaccharide (LPS, endotoxin) induces pancreatic injury on pancreatic acinar cells both in vivo and in vitro. Wistar male rats were treated with four intraperitoneal injections of 10 mg/kg LPS, and AR4-2J cells were exposed to increasing doses of LPS. Expression of pancreatitis-associated-protein (PAP) mRNA was strongly induced in AR4-2J cells exposed to LPS, while amylase mRNA was reduced. LPS also induced apoptosis and expression of TNF-alpha, IL-1beta, and IL-8 mRNA in AR4-2J cells. The in vivo effect of LPS showed structural signs of cellular damage, including numerous cytoplasmic vacuoles, severe nuclear alterations, and high expression of PAP mRNA. This study demonstrated that LPS induced pancreatic damage by directly affecting the pancreatic acinar cells. The role of LPS in the pathophysiology of acute pancreatitis may be partly due to the effect LPS has on the acinar cell.
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PMID:Lipopolysaccharide directly affects pancreatic acinar cells: implications on acute pancreatitis pathophysiology. 1079 55

Recently, there has been a great deal of interest in the role of cytokines in acute pancreatitis. Serum levels of IL-1, IL-6, and TNF-alpha have been demonstrated to be elevated in acute pancreatitis. We hypothesized that cytokines may be produced primarily by pancreatic parenchymal cells. Reasoning that ductal epithelium is the cell type most likely to be exposed to noxious stimuli in common causes of pancreatitis, such as ERCP and passage of a gallstone, we examined the response of well differentiated pancreatic ductal adenocarcinoma cell lines to stimuli known to stimulate cytokine production in other cells. CAPAN-1 and CAPAN-2 cells were incubated with endotoxin or TNF-alpha. The supernatant was assayed for production of IL-1, IL-6, and IL-8 by ELISA. The cells were assayed for activation of the transcription factor NF-kappaB by electrophoretic mobility shift assay. There was no detectable production of IL-1 by either cell line. CAPAN-1 cells had concentration-dependent production of IL-6 and IL-8 in response to both endotoxin and TNF-alpha. CAPAN-2 cells had concentration-dependent production of IL-6 and IL-8 in response to TNF-alpha. They had low level expression of IL-8 that was unaffected by any concentration of LPS, and no detectable production of IL-6 in response to LPS. These findings suggest that pancreatic duct cells may take an active part in the pathogenesis of acute pancreatitis through the production of cytokines.
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PMID:Cytokine production by CAPAN-1 and CAPAN-2 cell lines. 1079 56

Acute pancreatitis is a disorder that has numerous causes and an obscure pathogenesis. Bile duct stones and alcohol abuse together account for about 80% of acute pancreatitis. Most episodes of biliary pancreatitis are associated with transient impaction of the stone in the ampulla (that causes obstruction of the pancreatic duct, with ductal hypertension) or passage of the stone though and into the duodenum. Other causes of acute pancreatitis are various toxins, drugs, other obstructive causes (such as malignancy or fibrotic sphincter of Oddi), metabolic abnormalities, trauma, ischemia, infection, autoimmune diseases, etc. In 10% of cases of acute pancreatitis, no underlying cause can be identified; this is idiopathic pancreatitis. Occult biliary microlithiasis may be the cause of two thirds of the cases of "idiopathic" acute pancreatitis. Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis, resulting in subsequent activation of other proteases causing the subsequent cell damage. Ischemia/reperfusion injury is increasingly recognized as a common and important mechanism in the pathogenesis of acute pancreatitis and especially in the progression from mild edematous to severe necrotizing form. Increased intracellular calcium concentration also mediates acinar cell damage. Oxygen-derived free radicals and many cytokines (e.g., interleukin [IL]-1, IL-6, IL-8, tumor necrosis factor-alpha, platelet activating factor) are considered to be principal mediators in the transformation of acute pancreatitis from a local inflammatory process into a multiorgan illness.
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PMID:Etiology and pathogenesis of acute pancreatitis: current concepts. 1087 61

Multi-organ dysfunction syndrome (MODS) is the primary cause of morbidity and mortality in acute pancreatitis. Recent studies have established the critical role played by inflammatory mediators such as TNFalpha, IL-1beta, IL-6, IL-8, CINC/GROalpha, PAF, IL-10, C5a, ICAM-1 and substance P in acute pancreatitis and the resultant MODS. Potentially, there is a therapeutic window between symptom onset and the development of distant organ damage, when anti-inflammatory therapy may be of use. Elucidation of the key mediators in acute pancreatitis coupled with the discovery of specific inhibitors may make it possible to develop clinically effective anti-inflammatory therapy.
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PMID:Inflammatory mediators as therapeutic targets in acute pancreatitis. 1156 5

Interleukin (IL) -6 and IL-8 are cytokines that have been shown to play a role in several pancreatic diseases, including acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma. Previously, we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) and gram-negative bacterial lipopolysaccharide stimulate production of IL-6 and IL-8 and activation of the transcription factor NF-kappaB in the well-differentiated pancreatic ductal adenocarcinoma cell lines CAPAN-1 and CAPAN-2. In these studies we have examined the effect of chain-breaking and glutathione-enhancing antioxidants on NF-kappaB activation and production of IL-6 and IL-8 in these cell lines. Generally, suppression of NF-kappaB activation correlated well with inhibition of IL-6 and IL-8 secretion. In the CAPAN-2 cell line, antioxidants inhibited both NF-kappaB activation and IL-6 and IL-8 secretion. In the CAPAN-1 cell line, antioxidants generally failed to suppress both NF-kappaB activation and IL-6 and IL-8 secretion. The single exception was the chain-breaking antioxidant butylated hydroxyanisole (BHA), which markedly inhibited IL-6 and IL-8 secretion, but had no effect on NF-kappaB activation. These findings may have implications for the treatment of acute and chronic pancreatitis and pancreatic cancer.
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PMID:Antioxidants inhibit cytokine production and suppress NF-kappaB activation in CAPAN-1 and CAPAN-2 cell lines. 1176 72


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