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)

We performed a case-control study to investigate the role of recent infection as stroke risk factor and to identify pathogenetic pathways linking infection and stroke. We examined 166 consecutive patients with acute cerebrovascular ischemia and 166 patients hospitalized for nonvascular and noninflammatory neurologic diseases. Control subjects were individually matched to patients for sex, age, and season of admission. We assessed special biochemical parameters in subgroups of stroke patients with and without recent infection (n = 21) who were similar with respect to demographic and clinical parameters. Infection within the preceding week was a risk factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1; 95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of recent infection and age were inversely related. Both bacterial and viral infection contributed to increased risk. Infection elevated the risk for cardioembolism and tended to increase the risk for arterioarterial embolism. Stroke patients with and without preceding infection were not different with respect to factor VII and factor VIII activity, fibrin monomer, fibrin D-dimer, von Willebrand factor, C4b-binding protein, protein S, anticardiolipin antibodies, interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor, interleukin-6, interleukin-8, and neopterin. In conclusion, recent infection is an independent risk factor for acute cerebrovascular ischemia. Its role appears to be more important in younger age groups. The pathogenetic linkage between infection and stroke is still insufficiently understood.
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PMID:Recent bacterial and viral infection is a risk factor for cerebrovascular ischemia: clinical and biochemical studies. 944 80

Interleukin-6 (IL-6) is a neurotrophic cytokine expressed in both neurons and glia. The present study shows that cerebral ischemia produced by permanent occlusion of the middle cerebral artery (MCAO) produces a dramatic increase in IL-6 bioactivity in the ischemic hemisphere within 2 hours of MCAO (167 +/- 55 IU versus sham: 50 +/- 35 IU), with further increases at 8 hours (3,456 +/- 1,162 IU) and 24 hours (6,088 +/- 1,772 IU). In a separate series of experiments, intracerebroventricular injection of recombinant IL-6 (3,100 or 31,000 IU) significantly reduced ischemic brain damage after MCAO (to 52% and 65% of controls, respectively). The large increase in endogenous IL-6 bioactivity in response to ischemia, together with the marked neuroprotection produced by exogenous IL-6 suggest that this cytokine is an important endogenous inhibitor of neuronal death during cerebral ischemia.
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PMID:Cerebral interleukin-6 is neuroprotective during permanent focal cerebral ischemia in the rat. 946 60

Vasoactive intestinal peptide (VIP) is a neuropeptide synthesized by immune cells that can modulate several immune aspects, including the function of cells involved in the inflammatory response, such as macrophages and monocytes. Production and release of cytokines by activated mononuclear phagocytes is an important event in the pathogenesis of ischemia-reperfusion injury. VIP has been shown to attenuate the deleterious consequences of this pathologic phenomenon. We have investigated the effects of VIP and PACAP38 on the production of interleukin-6 (IL-6), a proinflammatory cytokine, by endotoxin-activated murine macrophages. Both neuropeptides exhibit a dual effect on the IL-6 production by peritoneal macrophages. Whereas VIP and PACAP inhibit with similar dose-response curves the release of IL-6 from macrophages stimulated with a LPS dose range from 100 pg/mL to 10 microg/mL, both neuropeptides enhance IL-6 secretion in unstimulated macrophages and in macrophages stimulated with very low LPS concentrations (1-10 pg/mL). The inhibition on LPS-induced IL-6 production is specific, presumably mediated through a subtype of the PACAP-R. VIP and PACAP regulate the production of IL-6 at a transcriptional level. These results were correlated with an inhibition on both IL-6 expression and release in endotoxemic mice in vivo. These findings support the idea that in the absence of stimulation or in the presence of low doses of LPS, VIP and PACAP could play a role in immune system homeostasis. However, under toxicity conditions associated with high LPS doses, VIP and PACAP could act as protective mediators that regulate the excessive release of IL-6 in order to reduce inflammation or shock.
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PMID:Vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide modulate endotoxin-induced IL-6 production by murine peritoneal macrophages. 958 3

It has been shown in vitro that glycine can protect renal tubules and hepatocytes from hypoxic injury. Glycine also attenuates ischemic injury in transplanted livers. The present study investigated the effect of enteral glycine in a murine model of ischemia/reperfusion injury of the small intestine. Mice (n = 12 in each group) were randomized to receive two gastric gavages of either a 20% glycine (Gly) or 23% balanced amino acid (AA) solution with a 6-hour interval between each gavage. One hour after the second gavage, mice underwent superior mesenteric artery clamping for 20 minutes. The clamp was then released for reperfusion. Another group of mice (n = 8) underwent a sham operation and served as additional control animals. Six hours after ischemia/reperfusion, the mice were killed in order to assess the intestinal injury (intestinal protein content, mucosal disaccharidase activity, and intestinal histologic findings) and the systemic consequences (bacterial translocation, serum interleukin-6, and lung myeloperoxidase activity). A second set of mice (n = 55) underwent identical gavages and ischemia/reperfusion and they were followed for survival. Compared to AA, enteral glycine administered prior to intestinal ischemia/reperfusion injury significantly preserved mucosal indices and intestinal histology and decreased lung myeloperoxidase activity. Survival was also significantly increased in animals receiving glycine compared to AA control mice. These data suggest that enteral glycine supplementation may be beneficial in attenuating intestinal ischemia/reperfusion injury and its related systemic effects in this murine model.
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PMID:Beneficial effect of enteral glycine in intestinal ischemia/reperfusion injury. 983 70

We have demonstrated that the ischemia-induced apoptosis of neurons in the CA1 region of the rat hippocampus was prevented by either intracerebroventricular or intravenous infusion of pituitary adenylate cyclase-activating polypeptide (PACAP). However, the molecular mechanisms underlying the anti-apoptotic effect of PACAP remain to be determined. Within 3-6 h after ischemia, the activities of members of the mitogen-activated protein (MAP) kinase family, including extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), and p38 were increased in the hippocampus. The ischemic stress had a potent influence on the MAP kinase family, especially on JNK/SAPK. PACAP inhibited the activation of JNK/SAPK after ischemic stress. Secretion of interleukin-6 (IL-6) into the cerebrospinal fluid was intensely stimulated after PACAP infusion. IL-6 inhibited the activation of JNK/SAPK, while it activated ERK. These observations suggest that PACAP and IL-6 act to inhibit the JNK/SAPK signaling pathway, thereby protecting neurons against apoptosis.
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PMID:PACAP protects hippocampal neurons against apoptosis: involvement of JNK/SAPK signaling pathway. 992 3

Markedly increased interleukin-6 (IL-6) mRNA levels occur in experimental cerebral ischemia, although the protein production and cellular sources of IL-6 remain unclear. We examined the cellular localization of IL-6 protein in gerbil brain following transient forebrain ischemia employing immunohistochemistry and Western blot analysis. The ischemia/recirculation groups revealed distinct IL-6 immunoreactivity predominantly in cortical and hippocampal neurons after 3 hours to 3 days recirculation. At 12 h recirculation, the IL-6 expression declined specifically in the hippocampus CA1. Microglia, but not activated astrocytes, also expressed IL-6 immunoreactivity. The sham group showed no apparent immunoreactivity. IL-6 protein may thus be expressed mainly in neurons following transient forebrain ischemia. Its transient decline in the CA1 at 12 h recirculation could reflect the specific vulnerability of this region.
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PMID:Cerebral neurons express interleukin-6 after transient forebrain ischemia in gerbils. 1020 45

Interleukin-6 (IL-6) appears to be an important modulator of the inflammatory response associated with CNS ischemia. Clinically, IL-6 values obtained in the first week post-stroke have been shown to correlate with infarct size and outcome. In this study we used a focal reversible stroke model to investigate the time course and relationship to outcome of IL-6 production in plasma, brain and CSF. Reversible middle cerebral artery occlusion or sham surgery was produced in 50 adult Swiss Webster mice by advancing an 8-0 filament into the internal carotid artery for 2 h (sham 1 min). At 3, 6, 12, 24, and 72 h (8 each ischemia; 2 each sham) groups of animals were evaluated on a 28 point clinical scale, blood and CSF obtained, and the brains were evaluated for infarct volume and IL-6 mRNA levels. Serum levels of IL-6 (ELISA mean +/- SD; undetectable in controls) overall sham group, 102 +/- 87; 3 h, 908 +/- 494* pg ml-1; 6 h, 1079 +/- 468* pg ml-1; 12 h, 980 +/- 221* pg ml-1; pg ml-1; 24 h, 320 +/- 314* pg ml-1; 72 h, 20 +/- 30* pg ml-1 (*p < or = 0.05 to sham). CSF levels (ELISA) overall sham group, 10 +/- 18; 3 h, 379 +/- 210* pg ml-1; 6 h, 157 +/- 61* pg ml-1; 12 h, 136 +/- 88* pg ml-1; 24 h, 127 +/- 99 pg ml-1; 72 h, 72 +/- 9* pg ml-1 (*p < or = 0.05 to sham). Brain IL-6 mRNA levels overall sham group, 20; 3 h, 480; 6 h, 599; 12 h, 7960; 24 h, 20267; 72 h, 0. There was an overall R2 of 0.20 between plasma and CSF IL-6. There was an overall R2 of 0.13 and 0.20 between infarct size and serum and CSF IL-6 level respectively, and an overall R2 of 0.10 and 0.17 between neurologic function and serum and CSF IL-6 level respectively. These findings confirm that IL-6 values increase following CNS ischemia with peak serum and CSF levels occurring before brain values. CSF IL-6 levels had a stronger correlation with neurologic function and infarct size than serum.
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PMID:Time course of IL-6 expression in experimental CNS ischemia. 1031 38

To assess the adequacy of gastrointestinal mucosal perfusion perioperatively, the gastric intramucosal PCO2 (PiCO2) was monitored in ten patients undergoing elective coronary artery bypass grafting operation. Extracorporeal circulation was performed with mild hypothermia (temperature between 30 degrees C and 32 degrees C) and nonpulsatile flow. Plasma levels of interleukin-6 and endothelin-1 remained elevated up to twelve hours after surgery. The PiCO2 using the ion-sensitive field effect transistor (ISFET) sensor, attached to the tip of a nasogastric tube, increased significantly to 64 +/- 9 mmHg (mean +/- SD) at 6th postoperative hour from a baseline value of 48 +/- 7 mmHg. A similar trend was observed in PiCO2 as measured by capnographic gas tonometry. Although there was a close correlation between these two techniques (r2 = 0.4923), values with ISFET sensor were significantly higher (11-16 mmHg) than those by capnographic gas tonometry. Gastrointestinal mucosal ischemia, probably related to systemic inflammatory response, was observed during the immediate postoperative period. The PiCO2, measured directly and continuously with ISFET sensor, may be a more sensitive indicator compared with capnographic gas tonometry in evaluating the development of gastrointestinal mucosal injury.
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PMID:[Gastrointestinal ischemia in patients undergoing coronary artery bypass surgery--comparison of two methods for gastric intramucosal PCO2 monitoring]. 1040 9

Because neutrophil proteinases such as elastase and cathepsin G are considered to play a major role in inflammatory tissue damage, the microcirculatory effect of the serine proteinase inhibitor (serpin) Lex032 after ischemia/reperfusion (I/R)-induced pancreatitis was investigated. Lex032 inhibits these proteinases by recombinant combination of alpha(1)-antitrypsin and alpha(1)-antichymotrypsin. Twenty-eight anesthetized rats received either Lex032 or NaCl 0.9% as a control solution during baseline conditions or after 1 h of complete reversible ischemia induced by microclip occlusion of the pancreatic arteries. The number of erythrocyte-perfused capillaries (functional capillary density) and the leukocyte adherence in postcapillary venules were assessed by intravital microscopy 45, 90, and 120 min after administration. In the baseline group, Lex032 increased leukocyte adherence compared with the NaCl 0.9% baseline group, without changing any other parameter. I/R without Lex-032 treatment resulted in a 50% reduction in functional capillary density, a 2-fold increase in leukocyte adherence, an increase in interleukin-6 serum concentration, and a significant fall in blood pressure during reperfusion time compared with baseline animals. Treatment with Lex032 in I/R resulted in significant preservation of capillary perfusion, an absence of interleukin-6 increase, and preservation of mean arterial pressure during reperfusion time, without changing the leukocyte adherence, compared with the NaCl 0.9% I/R group. Because of its considerable amelioration of microcirculatory perfusion, Lex032 might be useful in the treatment of pancreatic I/R tissue damage (e.g., cardiac bypass surgery, pancreas transplantation, and hemorrhagic shock) by prevention of capillary perfusion failure.
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PMID:Inhibition of neutrophil proteinases by recombinant serpin Lex032 reduces capillary no-reflow in ischemia/reperfusion-induced acute pancreatitis. 1041 92

The effects of ischemia on the regenerative capacity of the liver after major tissue loss remain unclear. Interleukin-6 (IL-6) has been shown to confer protection in models of normothermic ischemia and reperfusion injury and to initiate hepatocyte proliferation after major hepatectomy. Therefore, we investigated the effects of ischemia on the regenerative capacity of the liver and evaluated the role of IL-6 in reducing reperfusion injury and enhancing hepatic proliferation in models combining ischemia and major hepatectomy. Rats subjected to 70% hepatectomy and 30 minutes of hepatic ischemia showed significantly reduced regenerative capacity (mitotic index, proliferating cell nuclear antigen, and regenerated liver weight) when compared with animals subjected to hepatectomy alone. Pretreatment of animals subjected to hepatectomy and ischemia with recombinant interleukin-6 (rIL-6) completely restored each parameter of regeneration to levels comparable with those of animals subjected to hepatectomy only. Similar results were obtained in IL-6 deficient (IL-6(-/-)) mice. IL-6(-/-) mice exposed to ischemia and hepatectomy showed impaired hepatic regeneration when compared with wild-type mice subjected to the same experimental conditions. The use of rIL-6 completely corrected each parameter of regeneration showing the specificity of IL-6 in this type of injury. The impact of IL-6 on animal survival was studied in a model combining 45 minutes of ischemia and 68% hepatectomy. Five of 7 (71%) animals pretreated with rIL-6 survived permanently, whereas all control animals died within 3 days of surgery (P =.02, Fisher's exact test). In conclusion, the study shows that ischemia dramatically impairs the regenerative capacity of the liver. IL-6 appears to be a key protective molecule in reducing injury and promoting regeneration following combined ischemia and major tissue loss.
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PMID:Ischemia impairs liver regeneration after major tissue loss in rodents: protective effects of interleukin-6. 1042 56


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