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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detectable TNF levels in sera 33% of patients with sepsis following pancreatitis have been found. No correlation was observed between serum TNF concentration and the severity of illness. However, monocytes and granulocytes of septic patients exerted higher TNF-mediated cytotoxicity than leukocytes of normal blood donors. The in vitro TNF-producing capacity was also higher in the patients in the study group, and it decreased only before fatal outcoming of sepsis. Our results suggest that determination of the TNF-producing capacity of leukocytes might be more informative than measurement of the serum TNF level in the evaluation of the severity or prognosis of sepsis.
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PMID:[Tumor necrosis factor production in septic conditions following pancreatitis (preliminary report)]. 173 28

Tumor necrosis factor-alpha (TNF alpha) is postulated to be a mediator of the systemic complications associated with acute pancreatitis. Neutralization of TNF alpha with monoclonal antibody ameliorates the morbidity and mortality associated with acute pancreatitis in a rat model. Although high levels of TNF alpha are measurable in peripheral blood in acute pancreatitis, specific sites of TNF alpha production in this disease have not been described. In this study we show that induction of pancreatitis causes up-regulation of TNF alpha messenger RNA (mRNA) at a distant organ site, the spleen. Hemisplenectomies were performed in male Sprague-Dawley rats prior to induction of pancreatitis by pancreatic duct infusion of artificial bile. Completion hemisplenectomies were then performed at 30 min, 1 hr, and 2 hr after pancreatitis induction. Quantitation of TNF alpha mRNA in the hemispleens before and after pancreatitis using a semiquantitative reverse transcriptase-polymerase chain reaction method revealed an 80-fold increase in amount of TNF alpha mRNA by 2 hr after induction of pancreatitis. By contrast, control rats receiving a sham operation showed no significant increase in TNF alpha mRNA expression after infusion of the pancreatic duct with saline. The increase in TNF alpha mRNA production was associated with increased serum TNF alpha product levels and was independent of endotoxin. We conclude that severe acute pancreatitis in the rat model is associated with significant up-regulation of TNF alpha mRNA in splenic mononuclear cells. These data provide evidence that the local events of acute pancreatitis can induce up-regulation of TNF alpha mRNA at a distant site and suggest a possible mechanism of pathogenesis of the systemic manifestations of this disease.
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PMID:Up-regulation of TNF alpha mRNA in the rat spleen following induction of acute pancreatitis. 853 66

The development of systemic complications in acute pancreatitis is largely responsible for the mortality associated with this disease. The systemic sequelae encountered in acute pancreatitis are similar to those occurring in patients with septic shock, a syndrome of multiple organ failure thought to be related to overproduction of inflammatory cytokines. As with sepsis, data is mounting that cytokines, particularly TNF alpha, may play a central role in acute pancreatitis and mediate the systemic sequelae of the disease. We have previously shown elevated levels of TNF alpha in the serum of animals with experimental acute pancreatitis. In this study, we use a bile-infusion model of pancreatitis in the rat to show amelioration of disease severity as well as a distinct survival advantage by TNF alpha blockade using anti-TNF alpha polyclonal antibody. These data provide strong evidence that TNF alpha is a major contributor to the morbidity and mortality from acute pancreatitis.
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PMID:Inhibition of TNF alpha improves survival in an experimental model of acute pancreatitis. 854 Jun 53

Tumor necrosis factor-alpha (TNF alpha) has been implicated as one of the numerous likely mediators of the systemic complications of acute pancreatitis. Recent suggestions that calcium (Ca2+) acts as a signal not only for TNF alpha release but also for TNF alpha action at distant sites led us to hypothesize that the calcium channel blocker diltiazem could inhibit TNF alpha release in acute pancreatitis, ameliorating the severity of the disease and improving overall survival. A rat model of acute pancreatitis induced by retrograde ductal infusion of bile was used for two experiments (n = 120). Experiment 1 was designed to determine the effects of calcium channel blockade using diltiazem on the severity of pancreatitis as measured by changes in biochemistry, pathology, and serum TNF alpha levels. In experiment 2, effects of calcium channel blockade on animal survival were measured over 72 h. Calcium channel blockade was associated with a significant reduction in serum TNF alpha levels as well as amelioration of pancreatitis by biochemical and pathological criteria. Overall survival from bile-induced pancreatitis was dramatically improved in rats pretreated with diltiazem (80%) compared to untreated animals (40%). Our data suggest that calcium channel blockade is associated with TNF alpha inhibition and improved outcome in a rat model of acute pancreatitis.
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PMID:Calcium channel blockade inhibits release of TNF alpha and improves survival in a rat model of acute pancreatitis. 878 30

Cytokines and their endogenous antagonists are released from inflammatory cells during acute pancreatitis, in particular its severe form. They can be found early in the course of the disease as is shown in animal models and in endoscopic retrograde cholangio-pancreatography (ERCP) induced human pancreatitis. Cytokine measurements can predict the course of the disease. This can, however, be achieved using more simple parameters, such as clinical judgement and leucocyte elastase. Anticytokine strategies in the treatment of severe acute pancreatitis should be further evaluated since some positive effects have been found in experimental settings. Interleukin 10 or soluble TNF alpha-receptors may be good candidates. Plasmapheresis seems to change cytokine-anticytokines patterns and this also needs to be explored in controlled trials.
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PMID:Interleukins in acute pancreatitis. 886 70

Activated leukocytes and cytokines have important roles in the multi-system involvement during acute pancreatitis. The changes in the serum level of tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) over time were investigated in two experimental acute pancreatitis models in rats. Mild edematous pancreatitis was induced with an overdose of cholecystokinin octapeptide (CCK-8), while a severe hemorrhagic form of pancreatitis was induced by ligation of the common bilio-pancreatic duct. The rats were examined 2, 4, 8, 16, 24 and 48 h after pancreatitis induction. The severity of the inflammation was assessed by measurement of the serum amylase activity, quantification of the edema, and histological examination. Serum TNF-alpha and IL-6 were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In CCK-8-induced acute pancreatitis, the pancreatic weight/body weight ratio (pw/bw) and amylase level were significantly elevated at 2 h, and the maximum levels were observed at 4 h (8.19 +/- 1.13 mg/g and 69.4 +/- 12.8 x 10(3) U/ml, respectively). Both parameters subsequently decreased continuously during the observation period. The serum IL-6 level was significantly increased at 4 h relative to the controls (123.3 +/- 5.8 vs 37.5 +/- 15 pg/ml), and then decreased continuously. In this model, only a moderate level of serum TNF-alpha was observed at 2 h. In the biliary type of acute pancreatitis, the ratio pw/bw increased continuously during the study and reached the maximum level at 48 h relative to the sham-operated control (8.8 +/- 1.4 vs 5.3 +/- 0.8 mg/g). The serum amylase level was significantly elevated at 2 h (43.2 +/- 13 x 10(3) U/ml), but then decreased continuously. The serum IL-6 reached its maximum level at 16 h (3800 +/- 447 pg/ml). In this model, increased TNF-alpha levels (75-300 U/ml) were measured 8, 16 and 24 h after pancreatitis induction. The results led to correlations between the serum IL-6 levels and the biochemical and morphological severity of acute pancreatitis in both experimental models. The data suggest that IL-6 and TNF-alpha may participate in the pathogenesis of these types of acute pancreatitis.
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PMID:Time-course changes in serum cytokine levels in two experimental acute pancreatitis models in rats. 887 1

The role of different cytokines in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, and the ability of KSG-504, a novel cholecystokinin receptor antagonist, to exert protection in this type of acute pancreatitis was evaluated. Male Wistar rats received 250 mg/100 g body weight of Arg intraperitoneally twice, at an interval of 1 h. Control rats received instead the same amount of glycine at the same times. Fifty mg/kg KSG-504 was injected subcutaneously 0.5 h before and 6, 18 and 36 h after the first Arg administration. Rats were examined 12, 24 and 48 h after pancreatitis induction. To assess the severity of inflammation, the edema was quantified, the serum amylase level was measured, and histologic examinations were performed. Serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were determined by bioassay, using the TNF-sensitive WEHI 164 and the IL-6-dependent B9 cell lines, respectively. In Arg-induced acute pancreatitis, the amylase level was increased significantly at 12 h (48.600 +/- 3.980 U/l) and 24 h (30.800 +/- 3.813 U/l) vs. the control group (6.382 +/- 184 U/l). No significant alteration in the ratio pancreatic weight/body weight was found in the different groups. However, in Arg-induced acute pancreatitis, both the TNF-alpha (15.1 +/- 6.9 U/ml) and the IL-6 (39.6 +/- 19.2 pg/ml) levels were already elevated significantly at 12 h vs. the controls (3.1 +/- 0.8 U/ml and 15.2 +/- 3.1 pg/ml, respectively) and remained elevated at 24 and 48 h. Simultaneous KSG-504 administration did not modify the measured cytokine levels. No significant changes in plasma CCK levels were observed. In Arg-induced acute pancreatitis, histological evaluation revealed diffuse but microfocal necrobiotic alterations. No marked protective effects of KSG-504 were observed on histological sections. These results suggest that excessive doses of Arg induce severe acute pancreatitis in rat, with a simultaneous cytokine level elevation. Endogenous CCK does not seem to play an essential role in the pathogenesis of Arg-induced acute pancreatitis.
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PMID:Cytokine level changes in L-arginine-induced acute pancreatitis in rat. 904 61

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.
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PMID:[Cellular and humoral functions in acute pancreatitis]. 913

The authors induced acute necrotizing pancreatitis in Wistar rat by intraductal injection of taurocholic acid (150 microliters or 200 microliters 6%). Plasma values of amylase, TNF, IL-6 levels and wet pancreas weight/body weight ratio have been determined. Histologic analysis of pancreas proved severe acute necrotizing pancreatitis with microabscess formation and beginning respiratory distress syndrome was observed in the lungs, TNF and IL-6 levels increased significantly after administration of 200 microliters 6% taurocholic acid. The authors emphasise the importance of cytokines in the development of acute necrotizing pancreatitis.
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PMID:[Cytokines in experimental acute pancreatitis]. 915 44

The purpose of this study was to evaluate the role of cytokines in septic conditions following acute pancreatitis and to elaborate a new strategy in the treatment. Increased TNF and IL-6 serum levels were found in 30% of the patients (n = 40), while the IL-6 level was elevated in all of them. There was a positive correlation between the serum IL-6 and sICAM-1 levels. The in vitro TNF and IL-6 producing capacities were initially higher in the study group, but decreased on subsequent days, especially in fatal cases (n = 3). Administration of pentoxifylline [PTX] (400 mg/day) to septic patients following necrotizing pancreatitis resulted in TNF and IL-6 production similar to that observed in control donors. The level of sICAM-1 also decreased following PTX therapy. These results suggest that cytokines produced by activated leucocytes are important in the pathogenesis of infected pancreatic necrosis, and their inhibition might be of therapeutic advantage.
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PMID:Relevance of cytokine production to infected pancreatic necrosis. 940 98


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