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)

Astrocytes have a critical role in the neuronal response to ischemia, as their production of neurotrophic mediators can favorably impact on the extreme sensitivity of nervous tissue to oxygen deprivation. Using a differential display method, a novel putative RNA binding protein, RA301, was cloned from reoxygenated astrocytes. Analysis of the deduced amino acid sequence showed two ribonucleoprotein domains and serine/arginine-rich domains, suggestive of their function as RNA splicing factor. Northern analysis displayed striking induction only in cultured astrocytes within 15 min of reoxygenation and reached a maximum by 60 min after hypoxia/reoxygenation. Immunoblotting demonstrated expression of an immunoreactive polypeptide of the expected molecular mass, 36 kDa, in lysates of hypoxia/reoxygenated astrocytes. Induction of RA301 mRNA was mediated, in large part, by endogenously generated reactive oxygen species, as shown by diphenyl iodonium, an inhibitor of neutrophil-type nicotinamide adenine dinucleotide phosphate oxidase which blocks oxygen-free radical formation by astrocytes. Similarly, increased expression of RA301 in supporting a neurotrophic function of astrocytes was suggested by inhibition of interleukin-6 elaboration, a neuroprotective cytokine, in the presence of antisense oligonucleotide for RA301. These studies provide a first step in characterizing a novel putative RNA binding protein, whose expression is induced by oxygen-free radicals generated during hypoxia/reoxygenation, and which may have an important role in redirection of biosynthetic events observed in the ischemic tissues.
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PMID:Cloning of a novel RNA binding polypeptide (RA301) induced by hypoxia/reoxygenation. 749 16

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous [SV]) for measurement of plasma endotoxin, 6-keto prostaglandin F1 alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-way ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05. Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic and colonic venous plasma eicosanoid and endotoxin concentrations, and colonic venous serum tumor necrosis factor and interleukin-6 activities in horses during low-flow ischemia and reperfusion of the large colon. 766 63

We have recently shown improved survival following intestinal ischemia-reperfusion in a model that utilized aggressive crystalloid resuscitation sufficient to eliminate reperfusion-induced cardiovascular instability. The aims of this study were to determine whether the salutary effects associated with this regimen were due to: 1) prevention of systemic metabolic derangements; 2) attenuation of secondary organ injury; or 3) modulation of the systemic immune response. Under anesthesia, 4-week-old (65-85 g) male Sprague-Dawley rats (N = 63) received crystalloids at either 15 or 65 ml.kg-1.h-1 intravenously and were subjected to 90 min of superior mesenteric artery occlusion followed by 90 min of reperfusion (IR15, IR65) or time-matched sham (SH) operation (SH15, SH65). Results indicate that inadequate fluid resuscitation following intestinal IR was associated with significant serum hyperkalemia and hyperphosphatemia, acute renal insufficiency, and enhanced serum interleukin-6 levels. Maintenance of cardiovascular stability with aggressive fluid resuscitation was associated with an attenuation of these alterations. Therefore, the prevention of circulatory shock and the attenuation of distant organ injury and inflammatory response are associated with improved survival when an aggressive crystalloid resuscitation regimen is applied after intestinal ischemiareperfusion in immature rats.
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PMID:Aggressive fluid resuscitation following intestinal ischemia-reperfusion in immature rats prevents metabolic derangements and down regulates interleukin-6 release. 774 42

The pathologic picture in ischemic tissue injury shares features with the inflammatory response, including production of proinflammatory cytokines. Hypoxia-mediated induction of interleukin-6 (IL-6), a cytokine with anti-inflammatory properties, could set in motion mechanisms limiting inflammation in ischemia. Exposure of cultured endothelial cells (ECs) to H (pO2 approximately 12-16 torr) increased transcription of IL-6, elevated levels of IL-6 mRNA, and induced elaboration of IL-6 antigen in a time-dependent manner. Exposure of mice to hypoxia increased IL-6 transcripts in the lung, and immunostaining revealed a striking increase in IL-6 antigen in pulmonary vasculature. Transfection of ECs with deletion chimeric IL-6 promoter-chloramphenicol acetyl-transferase (CAT) constructs showed hypoxia-mediated 9-11-fold induction with -1200/+13, -596/+13, and -225/+13 but no induction with -111/+13. Electrophoretic mobility shift assays (EMSAs) using -225/-111 as the labeled probe demonstrated enhanced binding activity in nuclear extracts of hypoxic ECs and lung; the appearance of the gel shift band was prevented by excess unlabeled probe (-225/-111), and hypoxia-mediated enhancement of the band was blocked by a probe corresponding to the nuclear factor (NF)-IL-6 site (-158/-145). The hypoxia-enhanced band on EMSA displayed a supershift with antibody to CCAAT-enhancer-binding protein beta (C/EBP-beta), but antibody to C/EBP-alpha or -delta was without effect. Transfection of ECs with a construct comprising thymidine kinase promoter, -225/-111 in either the 5' to 3' to 5' orientation, and the reporter CAT showed this region to be an enhancer (approximately 8-fold) under hypoxia. EMSA with the NF-IL-6 probe revealed a prominent induction of binding activity with nuclear extracts from hypoxic ECs and whole lung. Constructs with -158/-145 and the CAT reporter gene showed induction when transfected into hypoxic ECs, whereas a similar construct with the NF-IL-6 motif mutationally inactivated failed to display hypoxia-induced expression. Furthermore, the tumor necrosis factor (TNF) gene, whose product contributes to ischemic pathology and contains a putative regulatory NF-IL-6 site, demonstrated enhanced binding activity for its NF-IL-6 motif and induction of TNF mRNA based on analysis of hypoxic lung. These data indicate that hypoxia induces expression of IL-6, most likely a result of hypoxic activation at the NF-IL-6 site, and suggest that other genes with regulatory NF-IL-6 sites may also be induced by a similar mechanism.
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PMID:Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. 774 84

The expression of interleukin-6 (IL-6) mRNA in the focal ischemic rat cortex was studied by means of Northern hybridization. IL-6 mRNA was induced after permanent occlusion of the middle cerebral artery, reached a significant level at 3 h, and peaked at 12 h, i.e., approximately 10-fold increase in the ischemic zone compared with the nonischemic cortex or sham-operated controls. The increased IL-6 mRNA was elevated for at least 24 h. Low levels of IL-6 mRNA were detected in sham-operated rats or in the contralateral nonischemic cortex. The expression of c-fos and zif268 mRNAs, two early response genes, was rapid (increased by 1 h postischemia) and transient (returned to basal levels by 24 and 12 h, respectively), clearly having different kinetic patterns from that of IL-6 mRNA. The early response kinetic pattern of c-fos and zif268 mRNAs in focal ischemia suggests their transcriptional regulatory roles in response to ischemic insult, while the delayed induction pattern of IL-6 mRNA suggests a role for this pleiotropic cytokine in the inflammatory response to the focal ischemic damage of the brain.
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PMID:Expression of interleukin-6, c-fos, and zif268 mRNAs in rat ischemic cortex. 779 34

We examined the effect of interleukin-6 (human recombinant) on glutamate-induced neuronal death of cultured 20-day fetal rat hippocampal neurons. After 7 days in culture, the hippocampal neurons were markedly degenerated by the addition of L-glutamate and also N-methyl-D-aspartate. The neuronal death was prevented by the addition of MK801, a potent N-methyl-D-aspartate antagonist. Interleukin-6 at the concentration of 50 ng/ml has a significant preventive effect on the glutamate-induced neuronal death. Basic fibroblast growth factor at the concentration of 100 ng/ml gave also significant protective effect on hippocampal neurons, but nerve growth factor was ineffective in preventing the toxicity. It has been postulated that glutamate plays an important role in the pathogenesis of neuronal death such as ischemia and the various neurological diseases. Interleukin-6 might have somewhat physiological or pathological role in these events.
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PMID:Interleukin-6 protects cultured rat hippocampal neurons against glutamate-induced cell death. 791 97

Several studies have shown that the postoperative course of cytokines such as TNF-alpha or IL-6 is predictive of rejection and infection after human orthotopic liver transplantation (OLT). The aim of this prospective clinical trial was to evaluate the impact of transhepatic metabolism of endotoxin (ET), tumor necrosis-factor-alpha (TNF-alpha), and interleukin-6 (IL-6) after hepatic ischemia/reperfusion on the postoperative graft function. In 13 consecutive elective adult OLT patients with primary grafts, we determined concentrations of ET, TNF-alpha, and IL-6 in the radial artery, portal vein, and right hepatic vein at 1, 4, 7, 10, and 13 min after reperfusion. Of the 13 patients, four had ET levels below the detection limit (< 10 ng/L), and one patient had extremely high ET concentrations (151 ng/L in the hepatic vein). In the remaining patients the mean ET levels were 26 +/- 14, 26 +/- 15, and 24 +/- 14 ng/L in the portal vein, hepatic vein, and in the radial artery, respectively. These values indicate that in patients with a moderately elevated ET level, no transhepatic concentration differences of ET exist. However, in the patient with severe endotoxemia, the liver was apparently an ET-producing organ (HV-P: 29 +/- 13 ng/L). TNF-alpha levels were not measurable in four patients, and varied between 15 and 72 pg/ml (portal vein) in the remaining patients. The transhepatic concentration differences (HV-P and HV-A, respectively) of patients with PNF or dysfunction were higher than in those with "good" or "excellent" graft function (HV-P: 160 +/- 122 pg/ml vs. 7.3 +/- 9.7 pg/ml; P < 0.01 and HV-A: 137 +/- 101 pg/ml vs. 3.9 +/- 12 pg/ml; P < 0.01, respectively). Arterial IL-6 levels were below 88 pg/ml (mean value: 31 +/- 20 pg/ml) at the beginning of the operation, and increased considerably in three patients during the anhepatic phase and after reperfusion. No clinical correlation was found with the transhepatic concentration differences of IL-6. We conclude that in OLT patients without infection no transhepatic ET exchange was documented. However, a stimulated hepatic TNF-alpha release seems to be predictive of the beginning of liver dysfunction.
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PMID:Transhepatic metabolism of TNF-alpha, IL-6, and endotoxin in the early hepatic reperfusion period after human liver transplantation. 804 35

Ischaemia of the large bowel occasionally occurs following abdominal aortic aneurysm repair and may lead to multiple system organ failure (MSOF). Intramucosal acidosis of the sigmoid colon is a good indicator of sigmoid colonic ischaemia. Intramucosal pH of the sigmoid colon was measured using the silicone tonometer in 21 patients undergoing abdominal aortic aneurysmectomy. Samples were taken for plasma endotoxin, tumour necrosis factor (TNF) and interleukin-6 (IL-6) measurements preoperatively, half-hourly during the operation, 2-hourly for the next 12 h, 4-hourly for a further 48 h and 8-hourly thereafter until the fifth day. The intramucosal pH of the sigmoid colon fell to less than 7.00 peri-operatively in 10 patients, four of whom developed diarrhoea; in comparison, this did not occur in any of the 11 whose pH remained greater than 7.00 (p = 0.036). Higher peak concentrations of endotoxin, TNF and IL-6 were found in those patients whose intramucosal pH fell to less than 7.00 compared to those whose pH remained greater than 7.00 (mean +/- S.E.M. pg/ml, endotoxin = 112 +/- 24 vs. 58 +/- 6, p < 0.05; TNF = 26 +/- 8 vs. 7 +/- 2, p < 0.05; IL-6 = 213 +/- 59 vs. 87 +/- 12, p = 0.09). In the two patients who died, both from the group with pH level less than 7.00, concentrations of IL-6 were considerably higher than that in most of the other patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxaemia, the generation of the cytokines and their relationship to intramucosal acidosis of the sigmoid colon in elective abdominal aortic aneurysm repair. 840 98

Myocardial dysfunction following prolonged ischemia and reperfusion is at least partially dependent upon adhesion of neutrophils to myocardial and endothelial cells. Neutrophils are thought to contribute to reperfusion injury by two mechanisms: impairment of the microvasculature by physical obstruction, and secretion of products that damage microvasculature and myocardium. Cytokines have been shown to play several roles in neutrophil aggregation. Interleukin-6 (IL-6), along with IL-1 and tumor necrosis factor-alpha (TNF-alpha), induces the expression of intracellular adhesion molecule-1 (ICAM-1) in myocytes and endothelial cells, respectively. These cytokines also inhibit contractility and nitric oxide release (a vasodilator), and IL-1 and TNF-alpha have been found to reduce adrenergic stimulation of myocardial contractility by reducing intracellular cyclic AMP levels and uncoupling adenylate cyclase from beta receptors. The transforming growth factors, TGF-alpha and TGF-beta, also have a role in reperfusion injury. TGF-alpha reduces endothelial cell release of nitric oxide, while TGF-beta appears to protect against reperfusion injury by reducing plasma TGF-alpha levels, blocking neutrophil adherence, and promoting nitric oxide release. Although cytokines are likely to have important roles in reperfusion injury, their involvement in myocardial stunning is unclear.
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PMID:Cytokines and reperfusion injury. 846 22

Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interleukin-8. To elucidate the pathophysiology of this cytokine response, we explored the possible differences in cytokine responses between patients undergoing heart transplantation and those undergoing coronary artery bypass grafting. Plasma levels of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured in eight patients undergoing heart transplantation (mean age 44 years) and eight patients undergoing coronary artery bypass grafting (mean age 61 years). Duration of cardiopulmonary bypass and ischemic time were both longer in the heart transplantation group than in the coronary artery bypass grafting group (133 +/- 26 min vs 100 +/- 31 min, p < 0.05, and 130 +/- 47 min vs 58 +/- 21 min, p < 0.005, respectively). Samples were collected before heparin administration, at aortic crossclamping and declamping, and at 0.5, 1, 1.5, 2, 4, 12, and 24 hours after declamping. Tumor necrosis factor-alpha levels were significantly higher 30 minutes after aortic declamping in the heart transplantation group than in the coronary artery bypass grafting group (68 +/- 30 vs 18 +/- 5 pg/ml, p < 0.05). Interleukin-6 and interleukin-8 levels were also significantly higher 90 minutes after declamping in patients undergoing heart transplantation than in those undergoing coronary artery bypass grafting (310 +/- 63 vs 169 +/- 24 pg/ml, p < 0.05, and 73 +/- 17 vs 24 +/- 5 pg/ml, p < 0.01, respectively). Furthermore, interleukin-6 and interleukin-8 values 90 minutes after declamping were significantly correlated with the ischemic time (r = 0.72 and r = 0.82, respectively, both p < 0.05). Interleukin-10 levels in both groups rose to reach a peak value of around 115 pg/ml 1 hour after declamping. Patients undergoing heart transplantation exhibited a second peak of tumor necrosis factor-alpha, interleukin-8, and interleukin-10 levels 12 hours after declamping, probably related to the administration of rabbit antihuman thymocyte immunoglobulin (Thymoglobuline) 3 hours after declamping. Interleukin-6 levels decreased more significantly 12 and 24 hours after declamping in patients undergoing heart transplantation, probably related to methylprednisolone therapy. In conclusion, cardiopulmonary bypass is associated with the production of both proinflammatory and antiinflammatory cytokines. The production of proinflammatory cytokines in patients undergoing heart transplantation is higher than that in patients undergoing coronary artery bypass grafting, and this increase could be related to the longer duration of ischemia in the former group. The later course of cytokine levels after heart transplantation may be further influenced by immunosuppressive therapy.
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PMID:Human cytokine responses to cardiac transplantation and coronary artery bypass grafting. 875 37


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