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)

Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in sepsis. Bovine intestinal alkaline phosphatase (BIAP) was demonstrated to detoxify LPS through dephosphorylation. LPS injection combined with BIAP reduced inflammation and improved survival in various experimental settings. In this study, single-dose intravenous administration of BIAP (0.15 IU/g) was applied in a murine cecal ligation and puncture (CLP) model of polymicrobial sepsis. Saline was given as control (S group). Treatment with BIAP prior to CLP (prophylaxis; BIAP-P group) or shortly after (early treatment; BIAP-ET group) reduced cytokine concentrations in plasma and peritoneal lavage fluid (PLF). Tumor necrosis factor-alpha peak levels decreased from 170 pg/ml (S) to 57.5 (BIAP-P) and 82.5 (BIAP-ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (BIAP-P) and 16.8 (BIAP-ET) (all, P < 0.05). Peak interleukin-6 levels in plasma decreased from 19.3 ng/ml (S) to 3.4 (BIAP-P) and 11.5 (BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4 (BIAP-P) and 10.9 (BIAP-ET) (all, P < 0.05). Macrophage chemoattractant protein 1 peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (BIAP-P) and 0.7 (BIAP-ET) and in PLF from 6.4 (S) to 2.3 (BIAP-P) and 1.3 ng/ml (BIAP-ET) (all, P < 0.05). BIAP-treated groups showed decreased transaminase activity in plasma and decreased myeloperoxidase activity in the lung, indicating reduced associated hepatocellular and pulmonary damage. Survival was not significantly altered by BIAP in this single-dose regimen. In polymicrobial secondary peritonitis, both prophylactic and early BIAP treatment attenuates the inflammatory response both locally and systemically and reduces associated liver and lung damage.
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PMID:Bovine intestinal alkaline phosphatase attenuates the inflammatory response in secondary peritonitis in mice. 1597 24

The aim of this study was to investigate the influence of N-acetylcysteine (NAC) on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in significant increase in mortality rate, pancreatic necrosis and serum activity of amylase, alanine aspartate transferase (ALT), interleukin-6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, serum concentration of urea, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, and significant decrease of concentrations of calcium, blood pressure, urine output and pO(2). The use of NAC inhibited the changes in urine output, pO(2), tissue activity of MPO and MDA in pancreas and lungs, and the serum activity of IL-6, ALT, and serum concentrations of urea and calcium. NAC reduced the mortality and pancreatic damage. The use of NAC has a beneficial effect on the course of ANP in rats. It may be used in the treatment of acute pancreatitis.
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PMID:Effects of N-acetylcysteine on acute necrotizing pancreatitis in rats. 1608 83

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of kappaB-alpha, thereby suppressing proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.
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PMID:Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis. 1632 89

Recent studies have suggested that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavengers edaravone and tempol in the development of experimental dextran sulfate sodium (DSS)-induced colitis in mice. Male BALB/cA mice were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. Edaravone, tempol, or vehicle saline were then injected subcutaneously twice per day. After the experimental period, the colonic length, histological damage score, and mucosal myeloperoxidase (MPO) and serum interleukin-6 (IL-6) levels were measured. Edaravone (15 mg/kg/day) and tempol (5-15 mg/kg/day) suppressed the colonic shortening and the damage score. In particular, tempol at 15 mg/kg/day significantly attenuated the colonic shortening and damage score. Edaravone and tempol suppressed the serum IL-6 levels, and significantly suppressed the increased colonic MPO levels. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone and tempol in IBD patients is strongly expected.
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PMID:The free radical scavengers edaravone and tempol suppress experimental dextran sulfate sodium-induced colitis in mice. 1639 34

Dosing-time-dependent differences in lipopolysaccharide (LPS)-induced liver injury were examined in rats housed under a 12 h light : dark (LD) cycle. LPS (5 mg/kg) was intravenously injected into different groups of rats at 2, 14, or 20 h after light on (HALO). Elevations in serum liver enzymes after 14 HALO were significantly greater than those after 2 HALO. These parameters were lower in rats given LPS at 20 HALO, compared to 14 HALO. The number of polymorphonuclear cells (PMN) in the liver and the amount of hepatic myeloperoxidase activity, which reflects the number of PMN in liver tissues, was significantly greater in the 14 than in the 2 HALO group. In addition, hepatic interleukin-6 (IL-6) production in the 14 HALO group was enhanced compared to that in the 2 HALO trial. These results suggest that LPS-induced liver injury is greater during the early active than during the early resting period. Dosing-time-dependent variation in the accumulation of PMN in the liver and, potentially, subsequent IL-6 production in liver tissues might be involved in this phenomenon.
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PMID:Dosing-time-dependent differences in lipopolysaccharide-induced liver injury in rats. 1639 3

The aim of this study was to investigate the influence of U-74389G on acute necrotizing pancreatitis (ANP) induced by glycodeoxycholic acid in rats. The induction of ANP resulted in a significant increase in mortality rate, pancreatic necrosis, and serum levels of amylase, alanine aminotransferase, interleukin-6, tumor necrosis factor alpha, and urea, in lactate dehydrogenase levels in bronchoalveolar lavage fluid, and in the activities of myeloperoxidase and malondialdehyde in pancreas and lung tissue; a significant decrease was observed in serum calcium levels, blood pressure, urine output, and pO(2). The use of U-74389G inhibited the changes in serum urea, pO(2), and tissue levels of myeloperoxidase and malondialdehyde in pancreas and lungs. Moreover, it indicated a limited effect on the course of ANP in the rats and did not reduce mortality and pancreatic damage. Therefore, it may be used in the treatment of lung injury during acute pancreatitis.
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PMID:Effects of lazaroid U-74389G on acute necrotizing pancreatitis in rats. 1655 23

We investigated the protective role of aminoguanidine (AG) in rat liver injury induced by chronic biliary obstruction. Secondary biliary cirrhosis was induced by bile duct ligation for 14 days. Swiss albino rats were divided into three groups: Common bile duct ligated (CBDL) rats; Group A, CBDL rats treated with AG as Group B and simple laparotomy group known as the Sham group; Group C. Group B received 200 mg/kg of AG intraperitoneally daily throughout 14 days. The present data showed decreased gama glutamyl transferase (GGT), aspartate aminotransferase (AST), bilirubin and alanine aminotransferase (ALT) levels in the AG treated rats, when compared with CBDL rats (p < 0.05). In the AG treated rats, tissue levels of malondialdehyde (MDA) were significantly lower than that in CBDL rats (p < 0.001). Although the levels of glutathione (GSH) in AG treated rats were higher and myeloperoxidase (MPO) were lower than that in CBDL rats, the difference was not statistically significant (p > 0.05). The levels of interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) were significantly lower and although the levels of interleukin-6 (IL-6) were lower in AG treated rats than that in CBDL rats, the difference was not statistically significant. Administration of AG in the rats with biliary obstruction resulted in inhibition of ductular proliferation and portal inflammation. The present study demonstrates that intraperitoneal administration of AG in CBDL rats maintains antioxidant defenses, reduces liver oxidative and cytokine damage and ductular proliferation and portal inflammation. This effect of AG may be useful in the preservation of liver injury in cholestasis.
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PMID:The effect of aminoguanidine against cholestatic liver injury in rats. 1689 51

Posttraumatic activation of macrophages enhances development of systemic inflammation/immunosuppression and organ dysfunction. We hypothesized that Kupffer cells are the main source of monocyte chemoattractant protein-1 (MCP-1) production after trauma-hemorrhage, that administration of 17beta-estradiol (E2) after trauma-hemorrhage modulates MCP-1 release and reduces remote organ damage, and that salutary effects of E2 are mediated via estrogen receptor (ER)-alpha. To test these hypotheses, female B57BL/J6 mice received E2 (50 microg/25 g) or vehicle after trauma-hemorrhage and female 129 Sve ER-beta-/- transgenic mice and ovariectomized wild-type mice received E2 or ER-alpha agonist propyl pyrazole triol (50 microg/25 g) after trauma-hemorrhage. Systemic MCP-1 and interleukin-6 and their release by liver, spleen, and lung macrophages were determined by flow cytometry 4 hours after trauma-hemorrhage. Prior Kupffer cell depletion with gadolinium chloride significantly decreased systemic MCP-1 and interleukin-6 after trauma-hemorrhage and was associated with decreased edema/neutrophil infiltration in lung and liver. Kupffer cells were the only macrophages showing significant MCP-1 release, which was markedly reduced by E2 or propyl pyrazole triol in wild-type and in ER-beta-/- mice. Pretreatment of mice with anti-MCP-1 antiserum prevented an increase in myeloperoxidase and edema in lung and liver. These findings suggest that Kupffer cell-derived MCP-1 plays a major role in remote organ dysfunction after trauma-hemorrhage.
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PMID:Kupffer cells and their mediators: the culprits in producing distant organ damage after trauma-hemorrhage. 1693 55

Evidence indicates that the process of atherosclerosis has an inflammatory component. Markers of inflammation have been explored as a means for assessing (predicting) risk for the disease. Studies that evaluated the usefulness of fibrinogen, highly sensitive C-reactive protein, interleukin-6, myeloperoxidase, and soluble CD40 ligand for risk prediction are reviewed. Criteria for identifying a clinically useful test are discussed, along with the use of relative risk as a means for making clinically useful comparisons. It is concluded that clinically useful markers for routine screening and risk stratification have not been established, that prospective studies will be necessary to confirm the usefulness of current markers, and that on the basis of current knowledge, it will be a challenge to show that any of those inflammatory markers discussed herein will meet the needed criteria. Continued research into basic mechanisms by which inflammation acts in atherosclerosis may be necessary to identify useful markers for prediction.
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PMID:Inflammatory and long-term risk markers. 1693 84

The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity.
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PMID:Mechanisms of protection by melatonin against acetaminophen-induced liver injury in mice. 1694 81


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