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)

The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice, and caused a significant mortality (62%) only in the latter mice, indicating that interleukin-6 deficiency increased the susceptibility to kainic acid-induced brain damage. To compare the histopathological damage caused to the brain, control and interleukin-6 null mice were administered 8.75mg/kg kainic acid and were killed six days later. Morphological damage to the hippocampal field CA1-CA3 was seen after kainic acid treatment. Reactive astrogliosis and microgliosis were prominent in kainic acid-injected normal mice hippocampus, and clear signs of increased oxidative stress were evident. Thus, the immunoreactivity for inducible nitric oxide synthase, peroxynitrite-induced nitration of proteins and byproducts of fatty acid peroxidation were dramatically increased, as was that for metallothionein I+II, Mn-superoxide dismutase and Cu/Zn-superoxide dismutase. In accordance, a significant neuronal apoptosis was caused by kainic acid, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling and interleukin-1beta converting enzyme/Caspase-1 stainings. In kainic acid-injected interleukin-6 null mice, reactive astrogliosis and microgliosis were reduced, while morphological hippocampal damage, oxidative stress and apoptotic neuronal death were increased. Since metallothionein-I+II levels were lower, and those of inducible nitric oxide synthase higher, these concomitant changes are likely to contribute to the observed increased oxidative stress and neuronal death in the interleukin-6 null mice. The present results demonstrate that interleukin-6 deficiency increases neuronal injury and impairs the inflammatory response after kainic acid-induced seizures.
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PMID:Interleukin-6 deficiency reduces the brain inflammatory response and increases oxidative stress and neurodegeneration after kainic acid-induced seizures. 1118 44

Cerebrospinal fluid (CSF) and peripheral blood pleocytosis have been observed after epileptic seizures without any evidence of infections, but no systematic studies on the acute phase reaction in such patients have been performed. We have previously reported increased levels of interleukin-6 (IL-6) in patients with recent tonic--clonic seizures. Because IL-6 is a major inducer of the systemic acute phase reaction, we decided to study various indicators of inflammation in the blood as well as their correlation with plasma and CSF IL-6 levels. CSF and blood samples were studied from 37 patients with previously undiagnosed and untreated tonic-clonic seizures without any clinical evidence of systemic or central nervous system infections as well as from 40 controls. The mean peripheral blood and CSF-leukocyte counts were significantly higher in patients compared with controls ( 7.9 x 10(9)vs. 6.1 x 10(9), P= 0.002 and 1.9 x 10(6)vs. 1.1 x 10(6), P= 0.032, respectively). There was some indication of increased concentration of C-reactive protein (CRP) and no difference in haptoglobin levels. There was a significant correlation between plasma but not CSF IL-6 concentration and those of both B-leukocyte count ( r= 0.051, P= 0.009) and CRP ( r= 0.42, P= 0.009). Epileptic seizures provoke a production of cytokines such as IL-6 that may in turn cause an activation of the acute phase reaction. Thus, CSF pleocytosis and increase in some indicators of inflammation should not automatically be attributed to systemic or CNS infections in patients with acute seizures.
Seizure 2002 Jan
PMID:Indicators of inflammation after recent tonic-clonic epileptic seizures correlate with plasma interleukin-6 levels. 1188 59

A 27-year-old man presented with fever, convulsive seizure, and sudden impairment of consciousness. Magnetic resonance imaging (MRI) abnormalities were found in the bilateral thalami, including the brain stem and white matter. The possibility of a previous influenza A virus infection was considered, and cerebrospinal fluid cells and interleukin-6 were elevated. The MRI findings closely resembled those found in cases of childhood acute necrotizing encephalopathy (ANE). The present case suggests that adult influenza A virus-associated encephalitis/encephalopathy or ANE can occur during winter influenza epidemics.
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PMID:A case of adult influenza A virus-associated encephalitis: magnetic resonance imaging findings. 1211 48

A 15-month-old girl developed frequent seizures at the eruptive stage of exanthema subitum. The eruption persisted for 2 weeks. Serum immunoglobulin G antibody to human herpes virus type 6 (HHV-6) increased markedly. Interleukin-6 was elevated whereas HHV-6 deoxyribonucleic acid was not detected in cerebrospinal fluid. These findings suggest that immune-mediated reactions after HHV-6 infection rather than direct action of active HHV-6 are responsible for frequent seizures in this case.
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PMID:Frequent seizures with elevated interleukin-6 at the eruptive stage of exanthema subitum. 1261 74

The systemic symptoms associated with influenza infection are mainly attributable to cytokines. To elucidate whether the high incidence of creatine kinase elevation and febrile seizures in influenza infection could be related to cytokines, we examined the serum levels of creatine kinase and cytokines (interferon-alpha, interleukin-6, and tumor necrosis factor-alpha) in patients with influenza and other febrile illness. Among those in the influenza group, 12 of 43 patients demonstrated elevated levels of creatine kinase (more than 200 IU/L), whereas in the control group two of 14 patients demonstrated elevated creatine kinase levels. When age was limited to under 7 years, seven of 32 patients (21.9%) in the influenza group had febrile seizures, whereas one of seven patients (14.3%) had a seizure in the control group. The influenza group demonstrated significantly high levels of interferon-alpha and interleukin-6. There was no correlation between cytokine levels and duration of fever or serum creatine kinase levels. The number of patients with high levels of interferon-alpha (>400 pg/mL) was significantly larger in the febrile seizure group than in the control group (six of seven patients in the febrile seizure group, 16 of 36 in the control group; P < 0.05). The present findings suggest the possible contribution of interferon-alpha in the pathogenesis of febrile seizures.
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PMID:Possible contribution of interferon-alpha to febrile seizures in influenza. 1243 68

We report a 2-year-old boy who developed hemiconvulsion-hemiplegia syndrome with left-sided hemiplegia after a seizure lasting 35 minutes. The interleukin-6 level in the cerebrospinal fluid 2 hours after seizure onset was elevated to levels seen in patients with encephalitis. At 1 year after onset of the seizure, the patient remained hemiplegic on the left side, and magnetic resonance imaging showed severe right hemispheric atrophy. Acute changes seen on imaging studies and electroencephalograms in this patient were consistent with seizure-induced brain damage. Elevation of cerebrospinal fluid interleukin-6 may be related to the severe neurologic sequelae of our patient despite the relatively short seizure duration.
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PMID:Hemiconvulsion-hemiplegia syndrome and elevated interleukin-6: case report. 1250 51

Transgenic mice with glial fibrillary acidic protein (GFAP) promoter driven-astrocyte production of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) were used to determine whether the pre-existing production of these cytokines in vivo might modulate the sensitivity of neurons to excitotoxic agents. Low doses of kainic acid (5 mg/kg) that produced little or no behavioral or electroencephalogram (EEG) alterations in wild type or glial fibrillary acidic protein (GFAP)-TNF animals induced severe tonic-clonic seizures and death in GFAP-IL6 transgenic mice of 2 or 6 months of age. GFAP-IL6 mice were also significantly more sensitive to N-methyl-D-aspartate (NMDA)- but not pilocarpine-induced seizures. Kainic acid uptake in the brain of the GFAP-IL6 mice was higher in the cerebellum but not in other regions. Kainic acid binding in the brain of GFAP-IL6 mice had a similar distribution and density as wild type controls. In the hippocampus of GFAP-IL6 mice that survived low dose kainic acid, there was no change in the extent of either neurodegeneration or astrocytosis. Immunostaining revealed degenerative changes in gamma aminobutyric acid (GABA)- and parvalbumin-positive neurons in the hippocampus of 2-month-old GFAP-IL6 mice which progressed to the loss of these cells at 6 months of age. Thus, GFAP-IL6 but not GFAP-TNF mice showed markedly enhanced sensitivity to glutamatergic- but not cholinergic-induced seizures and lethality. This may relate, in part, to a compromise of inhibitory interneuron function. Therefore, pre-existing IL-6 production and inflammation in the central nervous system (CNS) not only causes spontaneous neurodegeneration but also synergizes with other neurotoxic insults to induce more severe acute functional neurological impairment.
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PMID:Profound increase in sensitivity to glutamatergic- but not cholinergic agonist-induced seizures in transgenic mice with astrocyte production of IL-6. 1283 60

The proinflammatory cytokines tumor necrosis factor (TNFalpha), interleukin-1 (IL-1alpha), and interleukin-6 (IL-6) have been associated with various models of hippocampal damage. To examine their role in initiation of an acute hippocampal injury response, 21-day-old male CD-1 mice received an acute intraperitoneal (i.p.) injection of trimethyltin hydroxide (TMT; 2.0 mg/kg) to produce necrosis of dentate granule neurons, astrocyte, and microglia reactivity. Tremors and intermittent seizures were evident at 24 hr. Intercellular adhesion molecule-1 (ICAM-1), glial fibrillary acidic protein (GFAP), anti-apoptotic TNFalpha-inducible early response gene (A-20), macrophage inflammatory protein (MIP)-1alpha, TNFalpha, IL-1alpha, IL-6, and caspase 3 mRNA levels were significantly elevated. Pretreatment with the antioxidant, ebselen, decreased ICAM-1, A-20, and TNFbeta elevations. Pentoxifylline blocked elevations in A-20 and decreased elevations in GFAP mRNA levels. Neither prevented histopathology or behavioral effects. Intracisternal injection of TNFalpha-neutralizing antibody significantly inhibited both behavioral effects and histopathology. RNase protection assays showed that TMT-induced elevations in mRNA levels for ICAM-1, A-20, GFAP, MIP-1alpha, IL-1alpha, TNFalpha, TNFbeta, and caspase 3 were blocked by anti-TNFalpha. These data demonstrate a significant role for TNFalpha in an acute neuro-injury in the absence of contribution from infiltrating cells. The cerebellum shows limited if any damage after TMT; however, in combination with the i.c.v. injection, elevations were seen in GFAP and in EB-22, a murine acute-phase response gene homologous to the alpha (1)-antichymotrypsin gene. Elevations were similar for artificial cerebral spinal fluid and anti-IL-1alpha, and significantly increased with anti-TNFalpha, anti-IL-6, or the combination of antibodies. Responses seen in the cerebellum suggest synergistic interactions between the baseline state of the cell and manipulations in the cytokine environment. Data suggests a role for TNFalpha in the pathogenesis of hippocampal injury induced by TMT.
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PMID:Differential modulation of hippocampal chemical-induced injury response by ebselen, pentoxifylline, and TNFalpha-, IL-1alpha-, and IL-6-neutralizing antibodies. 1289 37

Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.
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PMID:Central neuro-inflammatory gene response following soman exposure in the rat. 1295 Nov 90

In the present study, the susceptibility of knockout interleukin-6 (IL-6(-/-)) mice to various convulsant stimuli has been evaluated and compared with other three related mice strains. Animals were treated with chemical convulsants impairing the gamma-aminobutyric acid neurotransmission [pentylenetetrazole (PTZ), picrotoxin, bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), methyl-beta-carboline-3-carboxylate (beta-CCM)], enhancing glutamatergic neurotransmission [N-methyl-d-aspartate (NMDA), alpha-amino-3 hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainic acid (KA)] or a K(+)channel blocker [4-aminopyridine (4-AP)]. The behavioural changes of such convulsant stimuli on IL-6(-/-) were observed and compared with those observed in C57, IL-6(+/+) and DBA/2 mice. The occurrence of clonic and/or tonic seizures was scored and statistically analysed to observe possible differences on seizure susceptibility. The IL-6(-/-) mice exhibited significantly higher seizure susceptibility to PTZ, beta-CCM, DMCM, NMDA, AMPA and KA than did the other mice strains, with the exception of DBA/2 mice. This study demonstrates that IL-6(-/-) mice possess an increased susceptibility to some convulsant stimuli. In particular, the major convulsant effects produced by NMDA, AMPA and KA suggest that the excitatory amino acid system is more active in the central nervous system (CNS) of IL-6(-/-) mice. The present data suggest that IL-6(-/-) mice might be a valid novel epileptic model for the study of pathophysiology and pharmacology of epileptic seizures.
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PMID:Seizure susceptibility to various convulsant stimuli of knockout interleukin-6 mice. 1509 21


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