Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects in the central nervous system, including induction of fever and sleep and the release of several neuropeptides. We evaluated effects of IL-1 beta on inhibitory postsynaptic function at the gamma-aminobutyric acidA (GABAA) receptor. IL-1 (100 pg/ml to 10 ng/ml) augmented GABAA receptor function in cortical synaptic preparations. This effect of IL-1 was largely prevented by incubation with a specific IL-1 receptor antagonist. The related cytokines interleukin-6 and tumor necrosis factor did not augment GABA-dependent chloride transport. Similar enhancement of GABAA receptor function was observed in tissue prepared from mice previously injected intraperitoneally with IL-1 (1 microgram). Electrophysiological studies in cultured primary cortical neurons demonstrated that IL-1 enhanced the GABA-mediated increase in chloride permeability, whereas IL-1 alone produced no alterations in resting conductance. Behavioral studies indicated that IL-1 is similarly active in vivo; mice treated with IL-1 showed a decrease in open-field activity and an increase in the threshold for pentylenetetrazol-induced seizures. The interaction of IL-1 with GABAA receptors might account for the somnogenic and motor-depressant effects of this cytokine.
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PMID:Interleukin-1 augments gamma-aminobutyric acidA receptor function in brain. 184 88

The fit-1 gene gives rise to two different mRNA isoforms, which code for soluble (Fit-1S) and membrane-bound (Fit-1M) proteins related to the type I interleukin (IL)-1 receptor. To investigate IL-1 binding, we have synthesized and purified histidine-tagged polypeptides corresponding to Fit-1S and the extracellular domain of the type I IL-1 receptor using a vaccinia expression system. Fit-1S is shown to interact with IL-1 beta, but not with IL-1 alpha. However, Fit-1S binds IL-1 beta only with low affinity in contrast to the IL-1 receptor, suggesting that IL-1 beta is not a physiological ligand of Fit-1S. Moreover, expression of the membrane-bound protein Fit-1M in transiently transfected Jurkat cells did not result in activation of the transcription factor NF-kappa B following IL-1 beta treatment. However, a chimeric protein consisting of the extracellular domain of the type I IL-1 receptor and of the transmembrane and intracellular regions of Fit-1M stimulated NF-kappa B-dependent transcription as efficiently as the full-length type I IL-1 receptor. These data indicate that Fit-1M is a signaling molecule belonging to the IL-1 receptor family.
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PMID:Low affinity binding of interleukin-1 beta and intracellular signaling via NF-kappa B identify Fit-1 as a distant member of the interleukin-1 receptor family. 762 57

In a prospective study, 17 Brazilian patients with parenchymatous neurocysticercosis were monitored for a period of 12 months after treatment with praziquantel. Taenia solium-specific IgG antibodies, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha, neopterin, and soluble interleukin-2 receptor (sIL-2R) were measured in serum and CSF before starting the therapy, on the last day of treatment, 5 weeks after treatment, and 3, 6, and 12 months after treatment. The most common symptoms and signs found in patients before treatment were headache, neck stiffness, and seizures. Six months after commencement of therapy, 13 of the 17 patients were free of complaints. Clinical normalization was paralleled by a significant decrease (p < 0.05) in the amount of intrathecally produced anti-T solium IgG 1 year after treatment. IL-1 beta was undetectable in serum at all times, whereas in the CSF it was within the normal range during the whole study period. The mean concentration of sIL-2R in the CSF was 65 kU/l (normal, < 50 kU/l) 5 weeks after treatment, whereas in all subsequent investigations sIL-2R was undetectable. The median CSF neopterin level was slightly elevated before treatment (6.8 nmol/l). One year after treatment, it had dropped by 69% (p < 0.001) to a median value of 2.1 nmol/l. The size of planimetrically measured focal cystic brain lesions on CT correlated with the amount of intrathecally synthesized anti-T solium IgG at the end of the study (r = 0.89, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and immunologic follow-up study of patients with neurocysticercosis after treatment with praziquantel. 890 70

Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of seizures. A common side effect of PHT therapy is gingival hyperplasia, occasionally so severe that it requires surgical intervention. Cyclosporine A (CSA) is a drug widely used for the control of rejection phenomena following solid organ and bone marrow transplantation. A frequent side effect of CSA administration is gingival overgrowth. As yet, the molecular mechanisms of drug-induced gingival hyperplasia are unknown although it has been postulated that certain drugs increase fibroblastic activity through alterations in levels of various growth factors and cytokines. The purpose of this study was to: 1) evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and interleukin (IL)-1 beta production in vitro after exposure to CSA; 2) determine the levels of PDGF-B and IL-1 beta gene expression in minimally inflamed gingival tissues of control patients and PHT-treated patients exhibiting gingival overgrowth as well as patients with severe gingival inflammation; and 3) combine characterization of macrophage phenotype with clinical presentation and expression of PDGF-B and IL-1 beta in gingival tissues from the control and PHT-treated patients. For the in vitro studies, commercial ELISA kits were used to measure PDGF-A/PDGF-B and IL-1 beta levels in conditioned media from rat and human monocyte/macrophage cell cultures. CSA caused a significant elevation of PDGF but did not cause any changes in IL-1 beta levels. For the in vivo studies, quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B and IL-1 beta mRNA levels in experimental groups. PHT-treated patients exhibiting gingival overgrowth demonstrated a significant increase in PDGF-B mRNA compared with minimally inflamed controls. Patients with severe gingival inflammation also demonstrated a significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is approximately 6 times larger than PDGF-B upregulation produced by inflammation alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no significant increase in IL-1 beta mRNA; however, IL-1 beta mRNA levels in the severely inflamed gingival samples demonstrated a significant increase. Additionally, for the clinical samples, macrophage phenotype was characterized immunohistochemically in adjacent sections using specific monoclonal antibodies for inflammatory and reparative/proliferative phenotypes. There were no significant differences in the numbers of either macrophage phenotype in minimally inflamed gingival tissues; however, in the severely inflamed tissue, there was a significant increase in the inflammatory macrophage phenotype and in the hyperplastic gingival tissue, there was a significant increase in the reparative/proliferative macrophage phenotype. The results of this investigation indicate that the clinical presentation of inflamed and hyperplastic gingival tissues is associated with specific macrophages phenotypes which express the pro-inflammatory cytokine IL-1 beta in inflamed tissues or the essential polypeptide growth factor PDGF-B in PHT-induced hyperplastic tissues.
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PMID:Phenytoin and cyclosporine A specifically regulate macrophage phenotype and expression of platelet-derived growth factor and interleukin-1 in vitro and in vivo: possible molecular mechanism of drug-induced gingival hyperplasia. 902 55

We investigated the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 beta), and IL-6 as proinflammatory cytokines in CSF to facilitate differentiation between acute encephalitis/encephalopathy and prolonged febrile seizures. We studied 20 children with prolonged febrile seizures and 23 with acute encephalitis/encephalopathy, including 8 with an acellular CSF. TNF-alpha, IL-1 beta, and IL-6 in CSF were measured by ELISA. We found that TNF-alpha, IL-1 beta, and IL-6 were undetectable in CSF of all children with prolonged febrile seizures and control subjects but that the concentrations of TNF-alpha was elevated in 11, of IL-1 alpha in 6, and of IL-6 in 17 of 23 children with acute encephalitis/encephalopathy. Twenty-two of 23 children with acute encephalitis/encephalopathy had elevated concentrations of one or more cytokine. Elevated concentrations of the CSF proinflammatory cytokines, TNF-alpha, IL-1 beta, and IL-6, indicate acute encephalitis/encephalopathy rather than febrile seizures.
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PMID:Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 in cerebrospinal fluid from children with prolonged febrile seizures. Comparison with acute encephalitis/encephalopathy. 948 63

Interleukin-1 (IL-1) exerts a number of diverse actions in the brain, and it is currently well accepted that it contributes to experimentally induced neurodegeneration. Much of this is based on studies using the IL-1 receptor antagonist, which inhibits cell death caused by ischemia, brain injury, or excitotoxins. Our aim is to determine how and where in the brain IL-1 acts to produce these effects. Most of the neurodegenerative effects of IL-1 are thought to be through IL-1 beta. However, we have data implicating IL-1 alpha in excitotoxic cell death. Furthermore mice lacking both IL-1 alpha and IL-1 beta show dramatically reduced ischemic cell death, whereas deletion of IL-1 alpha or IL-1 beta alone fails to modify damage. It has also been demonstrated that IL-1 exacerbates ischemic injury in mice in the absence of the type I IL-1 receptor, suggesting the existence of novel IL-1 receptors in the brain. IL-1 also dramatically exacerbates neuronal loss in response to intrastriatal administration of the excitotoxin AMPA in the rat brain, an effect accompanied by marked increases in cytokine expression in the frontoparietal cortex, which precedes subsequent cell death in this region. Intrastriatal AMPA also results in limbic seizures that are exacerbated by IL-1, and we hypothesize, therefore, that IL-1 exacerbates cell death through increased seizure activity. Therefore, IL-1 appears to induce acute neurodegeneration through a number of mechanisms.
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PMID:Interleukin-1 in the brain: mechanisms of action in acute neurodegeneration. 1279 45

Feline infectious peritonitis (FIP) is a progressive, fatal, predominantly Arthus-type immune-mediated disease that is triggered when cats are infected with a mutant enteric coronavirus. The disease presents variably with multiple organ failure, seizures, generalized effusion, or shock. Neurological FIP is clinically and pathologically more homogeneous than systemic 'wet' or 'dry' FIP; thus, comparison of cytokine profiles from cats with neurological FIP, wet FIP, and non-FIP neurological disease may provide insight into some baseline characteristics relating to the immunopathogenesis of neurological FIP. This study characterizes inflammation and changes in cytokines in the brain tissue of FIP-affected cats. Cellular infiltrates in cats with FIP included lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils. IL-1 beta, IL-6, IL-12, IL-18, TNF-alpha, macrophage inhibitory protein (MIP)-1 alpha, and RANTES showed no upregulation in the brains of control cats, moderate upregulation in neurological FIP cats, and very high upregulation in generalized FIP cats. Transcription of IFN-gamma appeared upregulated in cats with systemic FIP and slightly downregulated in neurological FIP. In most cytokines tested, variance was extremely high in generalized FIP and much less in neurological FIP. Principal components analysis was performed in order to find the least number of 'components' that would summarize the cytokine profiles in cats with neurological FIP. A large component of the variance (91.7%) was accounted for by levels of IL-6, MIP-1 alpha, and RANTES. These findings provide new insight into the immunopathogenesis of FIP and suggest targets for immune therapy of this disease.
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PMID:Inflammation and changes in cytokine levels in neurological feline infectious peritonitis. 1462

We investigated the activation of the IL-1 beta system and markers of adaptive immunity in rat brain during epileptogenesis using models of temporal lobe epilepsy (TLE). The same inflammatory markers were studied in rat chronic epileptic tissue and in human TLE with hippocampal sclerosis (HS). IL-1 beta was expressed by both activated microglia and astrocytes within 4 h from the onset of status epilepticus (SE) in forebrain areas recruited in epileptic activity; however, only astrocytes sustained inflammation during epileptogenesis. Activation of the IL-1 beta system during epileptogenesis was associated with neurodegeneration and blood-brain barrier breakdown. In rat and human chronic epileptic tissue, IL-1 beta and IL-1 receptor type 1 were broadly expressed by astrocytes, microglia and neurons. Granulocytes appeared transiently in rat brain during epileptogenesis while monocytes/macrophages were present in the hippocampus from 18 h after SE onset until chronic seizures develop, and they were found also in human TLE hippocampi. In rat and human epileptic tissue, only scarce B- and T-lymphocytes and NK cells were found mainly associated with microvessels. These data show that specific inflammatory pathways are chronically activated during epileptogenesis and they persist in chronic epileptic tissue, suggesting they may contribute to the etiopathogenesis of TLE.
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PMID:Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. 1793 73

Epileptic seizures are hypersynchronous, paroxystic and abnormal neuronal discharges. Epilepsies are characterized by diverse mechanisms involving alteration of excitatory and inhibitory neurotransmission that result in hyperexcitability of the central nervous system (CNS). Enhanced neuronal excitability can also be achieved by inflammatory processes, including the participation of cytokines, prostaglandins or kinins, molecules known to be involved in either triggering or in the establishment of inflammation. Multiple inductions of audiogenic seizures in the Wistar audiogenic rat (WAR) strain are a model of temporal lobe epilepsy (TLE), due to the recruitment of limbic areas such as hippocampus and amygdala. In this study we investigated the modulation of the B1 and B2 kinin receptors expression levels in neonatal WARs as well as in adult WARs subjected to the TLE model. The expression levels of pro-inflammatory (IL-1 beta) and anti-inflammatory (IL-10) cytokines were also evaluated, as well as cyclooxygenase (COX-2). Our results showed that the B1 and B2 kinin receptors mRNAs were up-regulated about 7- and 4-fold, respectively, in the hippocampus of kindled WARs. On the other hand, the expressions of the IL-1 beta, IL-10 and COX-2 were not related to the observed increase of expression of kinin receptors. Based on those results we believe that the B1 and B2 kinin receptors have a pivotal role in this model of TLE, although their participation is not related to an inflammatory process. We believe that kinin receptors in the CNS may act in seizure mechanisms by participating in a specific kininergic neurochemical pathway.
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PMID:Modulation of B1 and B2 kinin receptors expression levels in the hippocampus of rats after audiogenic kindling and with limbic recruitment, a model of temporal lobe epilepsy. 1818 27

Previous studies have examined the association of a single nucleotide polymorphism at the promoter region of interleukin 1B (IL-1 beta-511T) with temporal lobe epilepsy and febrile seizures susceptibility, but those studies have been inconclusive. Published studies up to March 2007 of temporal lobe epilepsy, febrile seizures and the IL-1 beta-511T single nucleotide polymorphism were identified by searches of Medline and Embase databases. Meta-analysis of temporal lobe epilepsy and febrile seizures case-control data were performed to assess the association of IL-1 beta-511T with temporal lobe epilepsy, temporal lobe epilepsy with hippocampal sclerosis, febrile seizures, and other epileptic disorders. Pooled odds ratios (OR) were estimated by means of a genetic-model-free approach. The quality of the included studies was assessed by a score. The results show a modest association (OR, 1.48; 95% confidence interval, 1.09-2.00; P = 0.01) between the IL-1 beta-511T polymorphism and temporal lobe epilepsy with hippocampal sclerosis.
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PMID:Association study between interleukin 1 beta gene and epileptic disorders: a HuGe review and meta-analysis. 1828 14


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