Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vitro treatment of human peripheral blood mononuclear cells (PBMNC) with proteolytic enzymes (bromelain, papain) and amylase leads to the production of large amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) in a time and dose dependent manner. Increased TNF-alpha and IL-6 production was already found after 4-6 hours of incubation, and plateau levels were reached after 12-16 hours. Plateau levels up to 1500 pg TNF-alpha/ml/10(6) PBMNC, 13000 pg IL-1 beta/ml/10(6) PBMNC, and 23000 pg IL-6/ml/10(6) PBMNC were observed. Control cultures contained below 35 pg/ml/10(6) PBMNC of TNF-alpha, IL-1 beta or IL-6. In contrast to TNF-alpha which was undetectable after more than 24 hours, peak levels of IL-1 beta and IL-6 were still present at 24 hours. After incubation of the enzyme solution for some hours at 56 degrees C the cytokine inducing capacity disappeared. Neutralization experiments with inactivating antibodies, radioimmunoassay, and western blotting after electrophoretic separation showed that the TNF-like activity found in the lytic assay was due to TNF-alpha. Interferon-alpha (IFN-alpha) and Interferon-gamma (IFN-gamma), which had no effect alone, synergistically increased TNF-alpha production when applied together with the enzymes. A commercial mixture of these enzymes (Wobenzym), which was also investigated, showed a similar concentration and time dependence, as well as synergism with the interferons. A synergistic effect on TNF-alpha production was also found with the enzymes and phorbol ester (PMA).
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PMID:Proteolytic enzymes and amylase induce cytokine production in human peripheral blood mononuclear cells in vitro. 752 14

In necrotizing pancreatitis a high interleukin-6 (IL-6) serum level has been proposed as a prognostic criterium. However, literature does not report any information about the role of IL-6 in the function of pancreatic acinar cells. Cholecystokinin, gastrin binding, amylase release and intracellular calcium measurement were performed on a rat pancreatoma cell line, AR4-2J, which has been recognized as a useful tool for studies on the long-term regulation of pancreatic acinar cells. The addition of IL-6 (400 pM) for 48hrs to the AR4-2J cells induced no change in the binding affinities but there was a 2 fold increase in the binding capacity of cholecytokinin (CCKA R) and gastrin (CCKB R) receptors. Although IL-6 treatment did not change directly the secretory capacity and did not activate the intracellular calcium mobilization of AR4-2J, it indirectly increased the sensitivity of the cells to the stimulation of amylase release and the intracellular calcium mobilization by cholecystokinin and gastrin. It is most likely this effect was due to the IL-6-induced increase in the numbers of CCKA R and CCKB R. Therefore this report suggests that the cytokine IL-6 acts on the CCK regulation of pancreatic enzyme secretion.
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PMID:Interleukin-6 regulation of CCK/gastrin receptors and amylase secretion in a rat pancreatic acinar cell line (AR4-2J). 753 49

It has been suggested that the severity of an attack of acute pancreatitis is related to the presence of intraglandular trypsinogen activation and that disease severity is also reflected by the degree of the acute-phase protein response. In this study we examine the relationships among amylase release, the degree of trypsinogen and prophospholipase A2 activation [as measured by urinary trypsinogen activation peptide (TAP) and prophospholipase A2 activation peptide (PLAP) concentrations], and the serum concentrations of the acute phase-protein C-reactive protein (CRP) and the principal mediator of the acute-phase protein response, interleukin-6 (IL-6). Twenty-four patients (14 mild and 10 severe attacks) were studied. Peak serum amylase concentrations were seen within 12 h and peak urinary TAP/creatinine (Cr) and PLAP/Cr ratios between 12 and 24 h after the onset of symptoms, preceding those of IL-6 and CRP. The integrated TAP/Cr and PLAP/Cr responses were significantly greater in those with severe disease [95% confidence internal (CI) = 106-259.6 pmol/mmol/h, p < 0.0008; and 95.1% CI = 462.2-3887 pmol/mmol/h, p < 0.003, respectively]. The integrated amylase response was not significantly greater in those with severe disease (95.6% CI = -415 to 832 IU/L/h, p < 0.14). There was a strong correlation among the integrated IL-6, TAP/Cr (r = 0.63, p < 0.01), and PLAP/Cr (r = 0.64, p < 0.01) responses but a poor correlation with the integrated amylase response (r = 0.19, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relationship between pancreatic enzyme release and activation and the acute-phase protein response in patients with acute pancreatitis. 754 Jul 60

In severe acute pancreatitis (SAP), the mechanisms leading to adult respiratory distress syndrome (ARDS) are usually attributed to the release of active enzymes and vasoactive substances from the pancreas. Thoracic duct drainage has been proposed as a means of removing the portion of these substances that drain through retroperitoneal lymphatics before they reach the systemic circulation. This technique was used in six patients with ARDS complicating SAP. The levels of proinflammatory cytokines (tumor necrosis factor-alpha [TNF alpha], interleukin-1 [IL-1], and interleukin-6 [IL-6]), neutrophil enzymes (myeloperoxidase and lactoferrin), and pancreatic enzymes (amylase, lipase and trypsin) were measured in plasma and lymph in the first 24 h of ARDS and then on Day 2, Day 4, and at the end of the drainage (Day 8). High plasma concentrations of these products were measured. A moderate lymph-to-plasma gradient was observed for IL-6, lipase, and trypsin, while similar levels in plasma and lymph were recorded for the other substances. Plasma levels of pancreatic enzymes were weakly correlated with the lung injury score and lymph level of cytokines. These results suggest that in patients with ARDS due to SAP, cytokines as well as pancreatic enzymes could contribute to the development of the lung injury, and that lymphatics are potential vectors of these mediators.
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PMID:Lymphatic release of cytokines during acute lung injury complicating severe pancreatitis. 758 88

A 26 kDa particulate protein is phosphorylated during stimulation of amylase secretion by a beta-adrenergic agonist in the rat parotid gland. Previous study has shown that PP2C phosphatase is involved in dephosphorylation of this 26 kDa protein [Yokoyama, N. et al. (1994) Biochem. Biophys. Res. Commun. 200, 497-503]. In this study, immunotransblot analysis using anti-PP2C phosphatase antibody showed that PP2C phosphatase was found prominently in the cystolic fractions and less in secretory granule membranes. When cells were stimulated by isoproterenol, cytosolic PP2C phosphatase activity increased to 145% at 5 min and returned to basal level at 30 min. Forskolin increased PP2C phosphatase activity. H89 inhibited increase of PP2C phosphatase activity following beta-adrenergic stimulation. These results suggest that PP2C phosphatase activity is regulated by cAMP-mediated signaling following beta-adrenergic stimulation and participates in dephosphorylation of this 26 kDa protein.
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PMID:PP2C phosphatase activity is coupled to cAMP-mediated pathway in rat parotid acinar cells. 852 47

The importance of interleukin-1beta (IL-1beta) in the pathogenesis of acute pancreatitis has been demonstrated by dramatic attenuation of pancreatic destruction and significant increases in survival when its actions are inhibited. The pancreas has been shown to be a major producer of IL-1beta during pancreatitis but the cell(s) of origin remains unknown. Hypothesizing that infiltrating leukocytes contribute substantially, the intrapancreatic production of IL-1beta was examined after specific leukocyte populations were manipulated in vivo prior to the induction of pancreatitis. Sixty-four adult male Swiss mice were assigned to one of four groups 48 hr prior to induction of pancreatitis: (1) PMN depletion via anti-murine PMN antiserum. [PMN-d], (2) macrophage (Mphi) depletion via anti-macrophage antiserum [Mphi-d], (3) PMN and Mphi depletion [PMN+Mphi-d], and (4) Immunocompetent Pancreatitis. Edematous pancreatitis was induced in all experimental groups by caerulein (50 microg/kg/hr ip X 4). Animals were sacrificed 6 hr after induction of pancreatitis with severity determined by blind histologic grading and serum amylase, lipase, and interleukin-6 (IL-6) levels. Intrapancreatic IL-1beta production was determined by immunohistochemistry and semiquantitative differential RT-PCR. Pancreatitis developed in all animals receiving caerulein; however, leukocyte-depleted animals showed significantly attenuated levels of serum amylase, lipase, and IL-6, as well as lower histologic severity scores. Similarly, pancreatitis induction in immunocompetent mice showed pancreatic infiltration of IL-1beta-producing cells, whereas the leukocyte-depleted animals had significantly decreased numbers (PMN+Mphi-d < Mphi-d < PMN-d). IL-1beta mRNA was upregulated in all animals developing pancreatitis with significantly lower levels seen in the leukocyte-depleted groups. We conclude that infiltrating leukocytes, both neutrophils and macrophages, are responsible for the majority of intrapancreatic IL-1beta production during acute pancreatitis. The elimination of leukocytes and their products, including IL-1beta, significantly decreases the severity of pancreatic destruction.
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PMID:Intrapancreatic interleukin-1beta gene expression by specific leukocyte populations during acute pancreatitis. 866 Dec 28

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

Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet. Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) mRNA and protein were detected within the pancreas early in the course of pancreatitis in both models, coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle. A significant delay between pancreatic and distant organ cytokine production was always observed. It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs.
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PMID:Tissue-specific cytokine production during experimental acute pancreatitis. A probable mechanism for distant organ dysfunction. 928 48

Plasma levels of interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta 1) were studied during cholecystokinin octapeptide (CCK-8)-induced regeneration after pancreas resection in rats. The weight of the pancreas and the DNA and protein contents increased significantly. The serum levels of TGF-beta 1 and IL-6 were increased significantly on days 7 and 14. There was no significant change in serum amylase levels. These findings indicate that cytokines such as TGF-beta 1 and IL-6 may play a role in the pathomechanism of pancreas regeneration.
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PMID:TGF-beta 1 and IL-6--new aspects in pancreas regeneration? 940 99


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