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

Expression of IL-10 transgene (tg) in pancreatic beta cells failed to induce autoimmune insulitis and diabetes in (BALB/c x NOD)F1 mice. However, IL-10-expressing tg littermates from backcrosses (N2 and N3) with NOD mice became diabetic at 5 to 10 weeks of age in an MHC-dependent manner. In this study, we tested the possibility that enhancement in frequency of islet antigen (Ag)-specific T cells overrides the protective effects of a diabetes-resistant genetic background and promotes diabetes in IL-10 tg (BALB/c x NOD)F1 mice. For this test, we introduced the IL-10 transgene into tg BDC2.5 mice expressing the islet Ag-specific Vbeta4 T cell repertoire by breeding Ins-IL-10+/BALB/c mice with BDC2.5 mice. The progeny (Ins-IL-10+/BALB/c x BDC2.5+)F1 mice doubly tg for IL-10 and Vbeta4 (BDC2.5) T cell repertoire, developed diabetes at 10 to 18 weeks of age with a much more aggressive T cell infiltrate in the pancreatic islets than in single tg mice. Surprisingly, these diabetic mice were free from acute pancreatitis but had apoptotic beta cells in the islet infiltrate. Conversely, mice tg for Vbeta4 (BDC2.5) T cell repertoire but not IL-10 had no diabetes and no apoptotic beta cells in the islet infiltrate. Therefore, an increase in the frequency of islet-specific T cells apparently overcomes the protection from diabetes by a resistant genetic background. Interestingly, N2 backcross mice doubly tg for Vbeta4 (BDC2.5) T cell repertoire and IL-10, compared to N2 backcross mice tg for IL-10 only, eventually became diabetic but with a delayed onset and reduced incidence of disease. These findings demonstrate that, along with IL-10, an increase in frequency of islet antigen-specific T cells (a) overrides the protective effect of genetic resistance to autoimmune diabetes in F1 mice and (b) delays the onset of an otherwise accelerated diabetes in (Ins-IL-10+/NOD)N2 backcross mice.
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PMID:Differential impact of T cell repertoire diversity in diabetes-prone or -resistant IL-10 transgenic mice. 1022 59

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

To clarify the role of cytokines and acinar cell apoptosis in the pathogenesis of acute pancreatitis, we investigated the expression of intrapancreatic cytokines and apoptosis-related molecules in mice after pancreatic duct ligation (PDL). From day 1 or 3 after PDL, the expression of interleukin-1alpha (IL-1alpha), IL-1beta, IL-1 receptor antagonist, IL-6, IL-10, and tumor necrosis factor (TNF-alpha) mRNA were up-regulated in the pancreas, suggesting that these cytokines may be involved in the development of pancreatitis after PDL. Acinar cell apoptosis was observed in the pancreas at rates of 0.13 +/- 0.03, 1.32 +/- 0.38, and 0.86 +/- 0.23% on days 1, 3, and 7 after PDL, respectively. Significant increases in intrapancreatic mRNA levels of TNF-alpha, Fas ligand (FasL), and IL-1beta-converting enzyme (ICE) were observed from day 3 after PDL with the appearance of acinar cell apoptosis. The serum amylase activity peaked on day 1 after PDL and gradually decreased on days 3 and 7 after PDL. These results suggest that acinar cell apoptosis induced after PDL may modulate the progression of acute pancreatitis by reducing the release of digestive enzymes and may therefore be a host defense mechanism, and that acinar cell apoptosis after PDL may be mediated by the TNF-alpha and/or Fas/FasL and ICE system.
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PMID:Cytokine expression and induction of acinar cell apoptosis after pancreatic duct ligation in mice. 1043 65

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

Severe acute pancreatitis (AP) is associated with both the local (pancreatic) release of cytokines and an elevation in their systemic plasma concentrations. This may lead to organ dysfunction and death of the patient. The aims of this study were to investigate the source(s) of systemic cytokine production during experimental AP. Forty-two rats were allocated to five groups (control, sham operation and saline injection, sham operation and gadolinium chloride injection, intraductal sodium-taurocholate infusion and saline injection, or intraductal sodium-taurocholate infusion and gadolinium chloride injection). Blood from the iliac artery, portal vein, and hepatic vein, along with tissue from the pancreas, liver, and lung, were collected. Serum levels of TNFalpha, IL-1beta, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay. Tissue mRNA for IL-1beta and IL-10 was assessed by reverse-transcription polymerase chain reaction. In untreated animals with AP, the lowest serum cytokine levels were found in the portal vein. In the hepatic vein, the levels of TNFalpha, IL-1beta, and IL-6 were higher. The highest serum levels were detected in the systemic circulation. In the gadolinium chloride-treated group, there was no increase in hepatic or systemic cytokine levels and less lung injury was observed. Extrapancreatic cytokine production from both the liver and the lung contributed significantly to systemic levels of TNFalpha, IL-1beta, IL-6, and IL-10 in this experimental model of AP.
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PMID:Kupffer cell blockade reduces hepatic and systemic cytokine levels and lung injury in hemorrhagic pancreatitis in rats. 1107 97

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

This work studied the effects of hydrocortisone treatment in experimental acute pancreatitis on cytokines, phospholipase A2, and breakdown products of arachidonic acid and survival. Edematous and necrotizing pancreatitis were induced in Wistar rats by cerulein hyperstimulation and retrograde intraductal infusion of sodium taurocholate, respectively. Hydrocortisone (10 mg/kg) was administered intravenously 10 minutes after induction of acute pancreatitis. Serum was assayed for phospholipase A2; interleukin (IL) 1beta, IL-6, IL-10, thromboxane B2; Prostaglandin E2; and leukotriene B4 at five different time points. A significant release of inflammatory mediators was seen only in the severe model. Hydrocortisone powerfully suppressed arachidonic acid breakdown products and only mildly attenuated the systemic increase of phospholipase A2 and pro- and antiinflammatory cytokines. The mortality rate after 72 hr in the severe model was 86%. Hydrocortisone treatment reduced mortality to 13% (P = 0.001; Fisher's exact test). Hydrocortisone seems to be effective in the treatment of the early systemic inflammatory response syndrome associated with severe acute pancreatitis.
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PMID:Hydrocortisone treatment of early SIRS in acute experimental pancreatitis. 1168 May 90

The activity of monocyte/lymphocyte system and the splanchnic circulation was investigated in acute pancreatitis. The splanchnic blood flow was characterised indirectly by gastric intramucosal pH changes, which strongly correlated with APACHE-II score, and predicted the bad prognosis. The high CD14/HLA-DR and CD14/CD16 coexpression, the low TNF-alpha production proved to be unfavourable prognostic factor in the early phase of the disease. The expression of IL-2, IL-10 and moderately of IL-4 was elevated, but the expression of INF gamma did not show significant alteration. The thrombocyte aggregation decreased in the early phase. There are bad prognostic signs if its level remains constantly low and ATP-release increases. The activity and index of phagocytosis were higher in comparison with controls, but these parameters were not increasable with higher cell concentration. The ROI production increased, and the increase in the fMLP and o'zymosan indicated LDCL seems to be unfavourable prognostic sign, which well correlated with the APACHE-II score.
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PMID:[Role of the monocye-lymphocye system and of endogenous mediators in the severity of acute pancreatitis and in development of its septic complications]. 1172 28

In a recent study we have demonstrated that interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) serum levels correlate positively with the severity of acute pancreatitis (AP), induced by bile acid injected into the pancreatic duct of rabbits. In this article we describe the effect of an IL-10 analogue IT9302 and a monoclonal anti-IL-8 (mon. IL-8) antibody on the content of several pro-inflammatory cytokines in the serum of rabbits, after induction of AP. We found that the serum content of inflammatory cytokines IL-8, IL-1beta, TNF-alpha and monocyte chemoattractant protein 1 (MCP-1) are increased during AP. Injection of IT9302 or mon. IL-8 antibody, diminish the concentration of these cytokines in the serum, with the exception that mon. IL-8 antibody actually increased the circulating level of MCP-1. In addition, intravenous administration of IT9302 increased the serum levels of IRAP, an IL-1beta receptor antagonistic cytokine. Furthermore, intravenous injection of mon. IL-8 antibody increased serum levels of IL-4. It can be concluded that both the human IL-10 analogue IT9302 and mon. IL-8 antibody are able to alter the pro-inflammatory cytokine levels in rabbits suffering from experimentally induced AP.
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PMID:Profiles of pro-inflammatory cytokines in the serum of rabbits after experimentally induced acute pancreatitis. 1188 71

Interleukin (IL)-10, a potent anti-inflammatory cytokine, limits the severity of acute pancreatitis and downregulates transforming growth factor (TGF)-beta release by inflammatory cells on stimulation. Proinflammatory mediators, reactive oxygen species, and TGF-beta can activate pancreatic stellate cells and their synthesis of collagen I and III. This study evaluates the role of endogenous IL-10 in the modulation of the regeneration phase following acute pancreatitis and in the development of pancreatic fibrosis. IL-10 knockout (KO) mice and their C57BL/6 controls were submitted to repeated courses (3/wk, during 6 wk, followed by 1 wk of recovery) of cerulein-induced acute pancreatitis. TGF-beta(1) release was measured on plasma, and its pancreatic expression was assessed by quantitative RT-PCR and immunohistochemistry. Intrapancreatic IL-10 gene expression was assessed by semiquantitative RT-PCR, and intrapancreatic collagen content was assessed by picrosirius staining. Activated stellate cells were detected by immunohistochemistry. S phase intrapancreatic cells were marked using tritiated thymidine labeling. After repeated acute pancreatitis, IL-10 KO mice had more severe histological lesions and fibrosis (intrapancreatic collagen content) than controls. TGF-beta(1) plasma levels, intrapancreatic transcription, and expression by ductal and interstitial cells, as well as the number of activated stellate cells, were significantly higher. IL-10 KO mice disclosed significantly fewer acinar cells in S phase, whereas the opposite was observed for pseudotubular cells. Endogenous IL-10 controls the regeneration phase and limits the severity of fibrosis and glandular atrophy induced by repeated episodes of acute pancreatitis in mice.
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PMID:Endogenous interleukin-10 modulates fibrosis and regeneration in experimental chronic pancreatitis. 1201 37


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