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)

For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.
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PMID:Modulation of the immune response by transforming growth factor beta. 148 57

I propose that central nervous system endothelial cells are directly or indirectly responsible for the brain pathology in hepatic encephalopathy, and that this damage to the central nervous system is mediated by specific cytokines and nitric oxide which activate endothelial cells and thereby alter their cell functions. Liver diseases are conditions characterized by high circulating levels of cytokines, namely interleukin-1, interleukin-6 and tumor necrosis factor. Interactions between these cytokines and central nervous system endothelial cells may trigger a cascade of events including enhanced blood-brain barrier permeability, brain edema, astrocyte alterations and gliosis. Cytokine-induced production of nitrogen reactive molecules by endothelial cells themselves may also lead to further cellular damage and neuronal dysfunction. This hypothesis may explain several characteristics of hepatic encephalopathy including reversibility, disease progression and clinical features. It also suggests potential ways of intervention.
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PMID:The role of central nervous system endothelial cell activation in the pathogenesis of hepatic encephalopathy. 867 59

Pancreatic encephalopathy is a severe complication of acute pancreatitis. Proinflammatory cytokines may play a role in the development of multi-organ failure during pancreatitis. In the present study, we measured the changes in the blood-brain barrier (BBB) permeability concomitantly with the determination of serum tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels in rats before, as well as 6, 24 and 48 h after the beginning of intraductal taurocholic acid-induced acute pancreatitis. Cytokine concentrations were measured in bioassays with specific cell lines (WEHI-164 for TNF and B-9 for IL-6), while the BBB permeability was determined for a small (sodium fluorescein, molecular weight (MW) 376 Da), and a large (Evans' blue-albumin, MW 67000 Da) tracer by spectrophotometry in the parietal cortex, hippocampus, striatum, cerebellum and medulla of rats. The serum TNF level was significantly (P < 0.05) increased 6 and 24 h after the induction of pancreatitis, while the IL-6 level increased after 24 and 48 h. A significant (P < 0.05) increase in BBB permeability for both tracers developed at 6 and 24 h in different brain regions of animals with acute pancreatitis. We conclude that cytokines, such as TNF and IL-6, may contribute to the vasogenic brain edema formation during acute pancreatitis.
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PMID:Experimental acute pancreatitis results in increased blood-brain barrier permeability in the rat: a potential role for tumor necrosis factor and interleukin 6. 953 Sep 27

A rare case of sarcoid meningoencephalitis with no systemic lesion is reported here. A 58-year old man was admitted experiencing dull headache and speech disturbance. He had never received a diagnosis of systemic sarcoidosis. On admission, neurological examination revealed dysarthria, a defect of the right-side visual field and accelerated right Achilles tendon reflex. A T2-weighted MRI showed a high-intensity signal in the white matter of the left parieto-occipital lobe surrounded by severe brain edema with a mass effect. The meninges around the lesion were enhanced by gadolinium, but no enhancement was observed in the basal portion. Angiotensin-converting enzyme (ACE) activities of cerebrospinal fluid (CSF) and serum were within normal range. The level of interleukin-6 in the CSF was slightly elevated. Chest X ray films and chest CT revealed no abnormal lesions. Whole body gallium scanning showed a hot region only in the intracranial lesion. A brain biopsy was performed. Histological examination revealed typical granuloma of sarcoidosis accompanied by microvasculitis and epithelioid cell granuloma without caseous necrosis. Oral administration of prednisolone improved all symptoms and MRI findings. These observations suggest that release of cytokines from macrophages and epithelioid cells, as well as disruption of the blood-brain barrier due to microvasculitis, are involved in the mechanism responsible for producing lesions of sarcoid meningoencephalitis.
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PMID:[A case of sarcoid meningoencephalitis with an isolated supratentorial lesion]. 1125 86

We addressed the incidence of influenza-associated acute encephalopathy, which is distinct from Reye syndrome, in children in Japan. Eighty-nine children with a mean age of 3.8 years were reported to have developed this disease during eight influenza seasons (December 1994-April 2002) in Hokkaido, Japan. None of them had received aspirin. Most of the patients rapidly became comatose with or without convulsions with a mean interval of 1.7 days from the onset of fever to the onset of central nervous system symptoms. Thirty-three (37.1%) patients died and 17 (19.1%) patients had neurological sequelae. A total of 53 (59.6%) cases were proved to have an influenza virus infection. Interleukin-6 and tumor necrosis factor-alpha were markedly elevated in serum and cerebrospinal fluid samples from two patients who died after a rapid, fulminant course. A post-mortem examination of one fatal case revealed vasogenic brain edema with generalized vasculopathy, suggesting that the generalized impairment of vascular endothelial cells caused by highly activated cytokines plays a central role in the pathophysiology of this disease. We conclude that influenza-associated acute encephalopathy may be an underestimated syndrome and is another reason to promote vaccination against influenza in infants and younger children.
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PMID:Influenza-associated acute encephalopathy in Japanese children in 1994-2002. 1516 92

Erythropoietin (EPO) has recently been shown to have a neuroprotective effect in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. We, therefore, tried to analyze how recombinant human erythropoietin (rhEPO) might effect the inflammation-related factors common to TBI: nuclear factor kappa B (NF-kappaB), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) in a rat TBI model. Male rats were given 0 or 5000 units/kg injections of rhEPO 1h post-injury and on days 1, 2 and 3 after surgery. Brain samples were extracted at 3 days after trauma. We measured NF-kappaB by electrophoretic mobility shift assay (EMSA); IL-1beta, TNF-alpha and IL-6 by enzyme-linked immunosorbent assay (ELISA); ICAM-1 by immunohistochemistry; brain edema by wet/dry method; blood-brain barrier (BBB) permeability by Evans blue extravasation and cortical apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. We found that NF-kappaB, pro-inflammatory cytokines and ICAM-1 were increased in all injured animals. In animals given rhEPO post-TBI, NF-kappaB, IL-1beta, TNF-alpha and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after rhEPO treatment. Administration of rhEPO reduced brain edema, BBB permeability and apoptotic cells in the injured brain. In conclusion, post-TBI rhEPO administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which rhEPO improves outcome following TBI.
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PMID:Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: a potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO). 1782 90

Although N-acetylcysteine (NAC) has been shown to be neuroprotective for traumatic brain injury (TBI), the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-kappaB) and inflammatory proteins such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1) after TBI. As a result, we found that NF-kappaB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-kappaB, IL-1beta, TNF-alpha, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.
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PMID:Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. 1848 65

Evidence suggests that inactivation of cell-damaging mechanisms and/or activation of cell-survival mechanisms may provide effective preventive or therapeutic interventions to reduce cerebral ischemia/reperfusion (I/R) injuries. Docosahexaenoic acid (DHA) is an essential polyunsaturated fatty acid in the central nervous system that has been shown to possess neuroprotective effects. We examined whether different preadministrative protocols of DHA have effects on brain injury after focal cerebral I/R and investigated the potential neuroactive mechanisms involved. Sprague-Dawley rats were intraperitoneally pretreated with DHA once 1 h or 3 days being subjected to focal cerebral I/R or daily for 6 weeks before being subjected to focal cerebral I/R. Reduction of brain infarction was found in all three DHA-pretreated groups. The beneficial effect of DHA on the treatment groups was accompanied by decreases in blood-brain barrier disruption, brain edema, malondialdehyde (MDA) production, inflammatory cell infiltration, interleukin-6 (IL-6) expression and caspase-3 activity. Elevation of antioxidative capacity, as evidenced by decreased MDA level and increased superoxide dismutase activity and glutathione level, was detected only in the chronic daily-administration group. The two single-administration groups showed increased phosphorylation of extracellular-signal-regulated kinase (ERK). Elevation of Bcl-2 expression was detected in the chronic daily-administration and 3-day-administration groups. In vitro study demonstrated that DHA attenuated IL-6 production from stimulated glial cells involving nuclear factor kappaB inactivation. Therefore, the data suggest that the neuroprotective mechanisms of DHA pretreatment are, in part, mediated by attenuating damaging mechanisms through reduction of cytotoxic factor production and by strengthening survival mechanisms through ERK-mediated and/or Bcl-2-mediated prosurvival cascade.
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PMID:Protective effect of docosahexaenoic acid against brain injury in ischemic rats. 1880 85

Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. The absence of Nrf2 function in mice resulted in exacerbated brain injury as shown by the increased severity of neurological deficit, apoptosis, and brain edema at 24h after TBI. This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.
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PMID:Role of Nrf2 in protection against traumatic brain injury in mice. 1912 83

Simvastatin, a cholesterol-lowering agent, has demonstrated neuroprotective effects against brain injury, but the underlying mechanisms remain unclear. This study was undertaken to evaluate the effect of simvastatin on the Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappaB) related signaling pathway and secondary brain injury in rats after traumatic brain injury (TBI). Adult male Wistar rats were divided into four groups: (1) Sham group (n=25); (2) Sham+vehicle group (n=25); (3) TBI+vehicle group (n=30); and (4) TBI+simvastatin group (n=30). Right parietal cortical contusion was made by using a weight-dropping method. In TBI+simvastatin group, simvastatin was administered orally at a dose of 37.5 mg/kg at 1 and 6 h after TBI. Brain samples were extracted at 24 h after trauma. As a result, we found that treatment with simvastatin markedly inhibited the mRNA and protein expressions of TLR4, NF-kappaB and the downstream inflammatory agents, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1). Administration of simvastatin following TBI significantly ameliorated the secondary brain damage, such as cortical apoptosis, brain edema, blood-brain barrier (BBB) impairment, and motor deficits. In conclusion, post-TBI simvastatin administration may attenuate TLR4/NF-kappaB-mediated inflammatory response in the injured rat brain, and this may be one mechanism by which simvastatin improves outcome following TBI.
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PMID:Simvastatin reduces secondary brain injury caused by cortical contusion in rats: possible involvement of TLR4/NF-kappaB pathway. 1916 37


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