Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past few years, evidence has accumulated that implicates proinflammatory cytokines as the mediators responsible for the escalation of acute pancreatitis into a multisystem disease. It has been shown that the degree of serum cytokine elevation, particularly the macrophage-derived cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha, correlates with the severity and outcome of acute pancreatitis. Interleukin-10 is an anti-inflammatory cytokine that inhibits cytokine production from the macrophage. The aim of this study was to determine whether interleukin-10 would decrease both the severity of acute pancreatitis and the level of circulating proinflammatory cytokines. Ninety female mice were divided into three equal groups. Group 1 (controls) received intraperitoneal saline solution. Groups 2 and 3 received intraperitoneal cerulein (50 mg/kg/hr) for 7 hours. In addition, group 3 was given 1500 units of intraperitoneal interleukin-10, beginning 1 hour after the induction of acute pancreatitis and every 3 hours thereafter. Animals were killed at 3-hour intervals. Blood samples were obtained for serum amylase and cytokine determinations (interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha). Pancreata were dissected free and fixed in formalin for blinded histologic scoring. Interleukin-10 reduced the serum levels of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and amylase in comparison to untreated animals with pancreatitis (P < 0.05). Pancreatic edema, necrosis, and inflammatory cell infiltrate were also reduced in those animals given interleukin-10 (P <0.05). Histologic score, serum cytokines, and amylase levels are elevated during acute pancreatitis. Interleukin-10 given therapeutically, that is, after the onset of acute pancreatitis, lessened the severity of disease, probably through inhibition of the macrophage. This was associated with a decrease in circulating cytokine levels.
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PMID:Interleukin-10 reduces circulating levels of serum cytokines in experimental pancreatitis. 983 43

To investigate whether interleukin-10, a potent anti-inflammatory cytokine, could have a therapeutic effect on rats on that were made pancreatitis by cerulein. Thirty Wistar Albino rats were randomized into sham, pancreatitis, and therapy groups (n = 10 in each). Nothing was applied to the sham group; pancreatitis by inject-ing cerulein (50 micro/g/kg/h) was induced in the pancreatitis and therapy groups. Interleukin-10 (10.000 U) was injected at 1 and 4 h after pancreatitis inductions in the therapy group. The rats were sacrificed at postoperative hour 24. The following parameters were investigated: the leukocyte count, blood glucose, amylase, lipase and tumor necrosis factor-alpha levels in the blood samples; histopathological search, and wet/dry weight ratios of the pancreas tissues. The ratio of wet/dry pancreatic tissue weight, serum tumor necrosis factor-alpha, amylase and lipase lev-els, and histologic damage scores in the pancreatitis and therapy groups were significantly higher when they were compared with the sham group(p < .01). However, all of these values were significantly lower in the therapy groups than in the pancreatitis group (p < .01). Interleukin-10 decreases pancreatic tissue injury induced by cerulein-induced pancreatitis in rats. Nevertheless, more experimental studies are needed to compare endogenous interleukin-10 with exogenous interleukin-10 effects before clinical usage of this drug.
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PMID:The effect of interleukin-10 on acute pancreatitis induced by cerulein in a rat experimental model. 1580 46

Biotechnology has enabled greater understanding of the cellular and molecular biology of acute pancreatitis and has offered the possibility of a new generation of biodrugs to treat this disease. The proteases inhibitor gabexate mesilate has proven to be effective for endoscopic retrograde cholangiopancreatography-induced pancreatitis but, given the low incidence of this condition, its cost-effectiveness has to be evaluated. Randomised controlled trials have shown no benefit for somatostatin or its analogue octreotide although some practitioners continue to use it to prevent organ damage and complicated disease. Antioxidant therapy has been thoroughly investigated in animal models but the results of large scale clinical trials are awaited. The use of kinin inhibitors is in its infancy and has not yet reached the clinic. Considerable interest has been engendered in nitric oxide (NO), firstly for its beneficial use in acute lung injury resulting from the multi-organ failure of acute pancreatitis and secondly, the possible benefits of NOS inhibition to prevent pancreatitic necrosis. Tumour necrosis factor antagonism and interleukin- 1 blockade are 2 therapies awaiting clinical trials because there is overwhelming evidence of their benefit in animal models. Interleukin-10, an anticytokine, may have similar benefits and has been shown to be beneficial in animal models when given as pretreatment. The only biodrug that has progressed to phase III clinical trials is the platelet-activating factor antagonist lexipafant. Successful phase II studies have been followed up by a phase III study indicating benefits in reduction of organ failure and pseudocyst formation and reduction in mortality when treatment is given within 48 hours of onset of the disease. Finally, prophylactic therapy with selected antibacterials in patients with predicted severe disease can reduce local complications and possibly mortality.
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PMID:Acute pancreatitis: an overview of emerging pharmacotherapy. 1802 Jun 8