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

Epigallocatechin-3-gallate (EGCG) is the most prominent catechin in green tea. EGCG has been shown to modulate numerous molecular targets in the setting of inflammation and cancer. These molecular targets have also been demonstrated to be important participants in reperfusion injury, hence this study examines the effects of EGCG in myocardial reperfusion injury. Male Wistar rats were subjected to myocardial ischemia (30 min) and reperfusion (up to 2 h). Rats were treated with EGCG (10 mg/kg intravenously) or with vehicle at the end of the ischemia period followed by a continuous infusion (EGCG 10 mg/kg/h) during the reperfusion period. In vehicle-treated rats, extensive myocardial injury was associated with tissue neutrophil infiltration as evaluated by myeloperoxidase activity, and elevated levels of plasma creatine phosphokinase. Vehicle-treated rats also demonstrated increased plasma levels of interleukin-6. These events were associated with cytosol degradation of inhibitor kappaB-alpha, activation of IkappaB kinase, phosphorylation of c-Jun, and subsequent activation of nuclear factor-kappaB and activator protein-1 in the infarcted heart. In vivo treatment with EGCG reduced myocardial damage and myeloperoxidase activity. Plasma IL-6 and creatine phosphokinase levels were decreased after EGCG administration. This beneficial effect of EGCG was associated with reduction of nuclear factor-kB and activator protein-1 DNA binding. The results of this study suggest that EGCG is beneficial for the treatment of reperfusion-induced myocardial damage by inhibition of the NF-kappaB and AP-1 pathway.
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PMID:Epigallocatechin, a green tea polyphenol, attenuates myocardial ischemia reperfusion injury in rats. 1550 83

Inflammation plays a pivotal role in atherosclerosis and coronary heart disease. Inflammatory processes of the coronary arterial wall are involved in plaque formation, progression and, finally, plaque instability consecutively leading to the clinical manifestations of stable coronary artery disease or acute coronary syndromes (unstable angina, non-ST elevation and ST elevation myocardial infarction). Acute coronary syndromes result from plaque rupture or erosion leading to local thrombus formation with consecutive necrosis of myocytes due to ischemia, which is associated with widespread and diffuse pancoronary and panmyocardial inflammation. Accordingly, markers of myocardial necrosis (e. g., cardiac troponins) do have crucial diagnostic and prognostic value. In case of troponin-negative acute coronary syndromes, however, markers of inflammation emerged as potentially useful tools for risk stratification. C-reactive protein has been shown to serve as a powerful predictor of future cardiovascular events following acute coronary syndromes, even if troponins are not (yet) positive. Moreover, a variety of pro- (soluble CD40 ligand, placental growth factor, interleukin-6, pregnancy-associated plasma protein A, myeloperoxidase, monocyte chemoattractant protein-1) and anti-inflammatory markers (interleukin-10, activin A) have been suggested to provide relevant prognostic information in patients with acute coronary syndrome. However, the clinical utility of these novel markers has not been established so far.
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PMID:[Acute coronary syndrome and inflammation. Biomarkers for diagnostics and risk stratification]. 1559 73

3,3',5,5'-Tetramethylbenzidine (TMB) is the most commonly used chromogen for horseradish peroxidase (HRP) and so its performance as an electrochemical substrate was evaluated. Measurements of HRP activity in solution were carried out by using an amperometric detector coupled to a flow injection analysis (FIA) system. The enzymatic product was easily detected at a potential of +0.1 V (vs. Ag-pseudoreference electrode) at a bare screen-printed electrode placed in a homemade electrochemical flow cell. A high flow rate (4.3 mL min(-1)) of 0.5 M H2SO4 was used to obtain repeatable signals and a short analysis time. The detection limit achieved after 15 min of incubation was 2x10(-14) M of HRP. The applicability of the amperometric detector to ELISAs was demonstrated by using a commercially available kit for the quantification of interleukin-6 (IL-6) without modifying the kit manufacturer's protocol or the reagents for this test.
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PMID:Amperometric detection in TMB/HRP-based assays. 1589 70

Statins exert favorable effects on lipoprotein metabolism but may also possess anti-inflammatory effects. Here, we explored the effects of atorvastatin in a model of adjuvant-induced arthritis in rat. Oral treatment with atorvastatin (1-10 mg/kg) from days 10 to 15 after arthritis induction caused inhibition of the increase in paw volume. Maximal inhibition occurred at a dose of 10 mg/kg. At this dose, atorvastatin markedly ameliorated the histopathological findings of joints obtained from day 16 of arthritic animals. This was mirrored by an effective blockade of neutrophil influx, as assessed by the tissue myeloperoxidase levels. The concentrations of the cytokines interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha and the chemokines CCL5 and CCL2 were significantly decreased in arthritic rats treated with atorvastatin. In contrast, the levels of interleukin-10 were enhanced by the drug treatment. The drug also prevented the hypernociception observed in the inflamed joints. These data clearly illustrate the therapeutic potential of a statin-sensitive pathway in inflammatory arthritis.
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PMID:Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvant-induced arthritis. 1597 Feb 84

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

Chronic genital tract inflammations are a frequent cause or at least a concomitant factor of male fertility disturbances. The diagnosis is difficult because of the mostly asymptomatic course of the disease. Therefore, determination of biochemical markers of inflammation in addition to the number of leucocytes in the seminal plasma has been recommended. The aim of the study was to find out whether determination of granulocyte elastase and interleukin-6 provide comparable and reliable results with regard to diagnosis of genital tract inflammation; in addition, the association between genital tract inflammation and semen quality should be evaluated with special focus on potentially disturbed sperm functions like sperm motility and DNA integrity. In a prospective study, the concentrations of interleukin-6 (IL-6) and granulocyte elastase were determined in seminal plasma samples from 340 patients to investigate the relationship with other parameters of genital tract inflammation such as the number of peroxidase-positive cells and conventional semen parameters. Microbiological investigations were included. As post-testicular inflammatory influences may cause sperm DNA damage, the correlation between IL-6 and elastase and DNA integrity was evaluated by the sperm chromatin structure assay. IL-6 and elastase were significantly correlated both with each other (P < 0.01) and the number of peroxidase-positive cells (P < 0.01). IL-6 showed a highly significant negative correlation with sperm vitality (P < 0.01) and a significant negative correlation with sperm motility (P < 0.05). Elastase concentrations were highly significantly associated with the number of peroxidase-positive cells (P < 0.01) and negatively correlated with sperm vitality (P < 0.01). Moreover, there were significantly negative correlations with sperm motility (P < 0.05), progressive motility according to WHO a quality (P < 0.05) as well as sperm morphology (P < 0.05). In addition, a significant negative correlation was observed between elastase concentrations and percentage of spermatozoa with intact DNA, which may suggest the use of anti-inflammatory treatment. It can be concluded that both IL-6 and granulocyte elastase are useful and suitable as markers for silent genital tract inflammation; in contrast to previous contributions there were clear correlations of IL-6 and granulocyte elastase with sperm parameters, the relationship of elastase with semen quality being more marked. Moreover, the results of the study confirm the need for a change of the threshold value of peroxidase-positive cells according to WHO definition to lower levels for definition of silent genital tract inflammation.
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PMID:Role of granulocyte elastase and interleukin-6 in the diagnosis of male genital tract inflammation. 1626 98

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


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