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)

Neurocysticercosis, caused by Taenia solium, is one of the most common causes of seizures worldwide. The symptoms result from granulomatous inflammation associated with dying cyst forms of the parasite. Although the invasive larvae can be killed by immune serum plus complement, immunity to the cyst stage depends on a cellular response. This dichotomous immune response is reminiscent of the extremes of the immune response associated with T helper 1 (Th1) and Th2 cytokine profiles. To characterize the cytokine response in cysticercosis, granulomas were removed from the peritoneal cavity of mice infected with Taenia crassiceps cysts and examined for cytokine message by in situ hybridization using 35S-labeled RNA probes. The granulomas were staged based on histologic appearance of the degenerating parasite. Message for gamma interferon (IFN-gamma) was identified by light microscopy in 11 of the 12 granulomas, and interleukin-2 (IL-2) message was identified in 9 of the 12. By laser scanning confocal microscopy, significantly increased IFN-gamma and IL-2 pixel intensity was identified in nearly all of the granulomas from early histologic stages. Message for IL-4 was seen in 6 of the 12 granulomas. Only granulomas with complete destruction of the parasite architecture displayed more than minimal amounts of IL-4 message by light microscopy, and only 2 of 12 granulomas had IL-4 pixel intensity significantly above background. Only minimal amounts of IL-10 message were detected in 4 of 11 granulomas. Thus, early granulomas in cysticercosis are predominantly associated with a Th1 response, whereas later granulomas, in which parasite destruction is complete, have a mixture of Th1 and IL-4. The Th1 response appears to play an important role both in the pathogenesis of disease as well as in the clearing of the parasites, with IL-4 involved in downregulation of the initial response.
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PMID:Granuloma cytokines in murine cysticercosis. 919 68

Neurocysticercosis (NCC) is a common neurological disorder especially in developing countries, caused by infection of the brain with encysted larvae of the tapeworm Taenia solium. Seizures are a common finding associated with this disease. The objective of the present study was to evaluate the correlation between the levels of various cytokines present in the cerebrospinal fluid (CSF) of patients with NCC and the severity of the disease. The levels of the cytokines IL-1ss, TNF-alpha, IL-5, IL-10 and IFN-gamma were determined in the CSF of 22 patients with active NCC, 13 patients with inactive NCC and 15 control subjects. CSF from patients with active NCC presented significantly higher IL-5 levels compared to control subjects. IL-5 and IL-10 levels in CSF from NCC patients with inflammatory CSF were significantly higher than those detected in non-inflammatory CSF. These results show a predominant Th2 lymphocyte activation in human NCC and also indicate the possible use of cytokines in the CSF as a marker for the differential diagnosis between inactive disease and the active form of NCC.
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PMID:Interleukin-5 and interleukin-10 are major cytokines in cerebrospinal fluid from patients with active neurocysticercosis. 1097 38

Immunization with the whole-cell pertussis vaccine (Pw), while effective at preventing whooping cough in infants, has been associated with local, systemic, and neuronal reactions, including fevers and convulsions in children. In contrast, the new acellular pertussis vaccines (Pa) have a considerably improved safety profile. The lack of an appropriate animal model has restricted investigations into the mechanisms by which neurological reactions are induced by vaccination. Here we describe a novel murine model wherein seizure-like behavioral changes are induced following parenteral administration of Pw. The proinflammatory cytokine interleukin-beta (IL-1beta), production of which has been associated with many neurodegenerative conditions, was significantly increased in the hippocampus and hypothalamus of vaccinated animals. Accompanying this change was a decrease in release of the inhibitory neurotransmitters gamma-aminobutyric acid and adenosine in the hippocampus. Seizure-like behavioral changes were significantly reduced following inhibition of IL-1beta production by the administration of an inhibitor of IL-1beta-converting enzyme and were almost completely abrogated in IL-1 receptor type I knockout mice. These results suggest a causal relationship between IL-1beta induction and convulsive behavior following Pw vaccination. Significantly, Pa neither increased IL-1beta nor induced behavioral changes in mice, but did induce the anti-inflammatory cytokine IL-10. In contrast, administration of active pertussis toxin and lipopolysaccharide, residual in Pw but absent from Pa, also induced convulsive activity. Our findings provide the first direct evidence of an immunological basis for pertussis vaccine reactogenicity and suggest that active bacterial toxins are responsible for the neurologic disturbances observed in children immunized with Pw.
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PMID:Whole-cell but not acellular pertussis vaccines induce convulsive activity in mice: evidence of a role for toxin-induced interleukin-1beta in a new murine model for analysis of neuronal side effects of vaccination. 1140 57

Seizure-related changes in function of the peripheral immune system, especially in its cell component are poorly recognized. In the present study, we examined the effect of seizures induced by intraperitoneal injection of kainate to mice and rats on weight of central and secondary immunological organs and metabolic activity of splenocytes (MTT test). In kainate-injected mice the production of cytokines: interleukin 2 (IL-2) and IL-10 was also estimated. Seventy two hours after kainate administration, the mice and rats showed a marked decrease in the thymus weight by 36% and 50%, respectively, whereas the spleen weight tended to decrease in rats only. Splenocytes of kainate-injected mice and rats showed significant increase in metabolic activity. The ability of splenocytes of kainate-injected mice to produce IL-2 and IL-10 was reduced but only the former effect reached statistical significance. The results suggest a decrease in T helper-cell dependent immunoreactivity and enhanced phagocytic activity of macrophages in kainate-treated rodents.
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PMID:Immunoreactivity in kainate model of epilepsy. 1199 75

The effects of kindled seizures elicited from sites in the left and right temporal lobes on mitogen-induced proliferation (LPS, Con A, PHA) and induction of representative TH1 (IFN-gamma) and TH2 (IL-10, IL-4) cytokines were determined in activated rat splenocytes. With reference to cell proliferation, the changes depended on the hemispheric side and location of kindling. Kindling of the left side mediated significant increase in cell proliferation by LPS. Left side kindling resulted in decreased cell proliferation by PHA. Although right side kindling showed no change when taken together, further analysis showed that the reduced proliferation by PHA was mediated when the pyriform cortex was kindled with no change from amygdaloid nuclei. Similar hemispheric polarization was observed in the production of IL-10 and IFN-gamma by Con A-stimulated splenocytes in left side kindled rats. Hence, kindled temporal lobe seizures induced changes in specific immune functions. These effects are not only lateralized but are also specific with respect to the particular region kindled. Since epileptic patients have altered immune functions, this report contributes to our understanding of this complex immune-brain cross-talk in epilepsy.
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PMID:Effects of hemispheric lateralization and site specificity on immune alterations induced by kindled temporal lobe seizures. 1248 May 1

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.
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PMID:Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. 1538 60

We examined metallothionein (MT)-induced neuroprotection during kainic acid (KA)-induced excitotoxicity by studying transgenic mice with MT-I overexpression (TgMT mice). KA induces epileptic seizures and hippocampal excitotoxicity, followed by inflammation and delayed brain damage. We show for the first time that even though TgMT mice were more susceptible to KA, the cerebral MT-I overexpression decreases the hippocampal inflammation and delayed neuronal degeneration and cell death as measured 3 days after KA administration. Hence, the proinflammatory responses of microglia/macrophages and lymphocytes and their expression of interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor-alpha and matrix metalloproteinases (MMP-3, MMP-9) were significantly reduced in hippocampi of TgMT mice relative to wild-type mice. Also by 3 days after KA, the TgMT mice showed significantly less delayed damage, such as oxidative stress (formation of nitrotyrosine, malondialdehyde, and 8-oxoguanine), neurodegeneration (neuronal accumulation of abnormal proteins), and apoptotic cell death (judged by TUNEL and activated caspase-3). This reduced bystander damage in TgMT mice could be due to antiinflammatory and antioxidant actions of MT-I but also to direct MT-I effects on the neurons, in that significant extracellular MT presence was detected. Furthermore, MT-I overexpression stimulated astroglia and increased immunostaining of antiinflammatory IL-10, growth factors, and neurotrophins (basic fibroblastic growth factor, transforming growth factor-beta, nerve growth factor, brain-derived neurotrophic factor, glial-derived neurotrophic factor) in hippocampus. Accordingly, MT-I has different functions that likely contribute to the increased neuron survival and improved CNS condition of TgMT mice. The data presented here add new insight into MT-induced neuroprotection and indicate that MT-I therapy could be used against neurological disorders.
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PMID:Metallothionein reduces central nervous system inflammation, neurodegeneration, and cell death following kainic acid-induced epileptic seizures. 1561 85

It is well known that an acute encephalopathy occasionally follows prolonged febrile seizures. We measured the concentrations of interferon-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and soluble TNF receptor 1 (sTNFR1) in serum and CSF during the acute stage in 13 children with acute encephalopathy following prolonged febrile seizures (AEPFS) and 23 with prolonged febrile seizures without encephalopathy (PFS) to investigate the pathogenesis of AEPFS. Serum IL-6, IL-10, sTNFR1, and CSF IL-6 levels were significantly higher in AEPFS and PFS compared with control subjects. CSF IL-6 levels in AEPFS were significantly higher than those in PFS, but not serum IL-6, IL-10, or sTNFR1. The CSF IL-6 levels were significantly higher than the serum levels in AEPFS, but not PFS. The serum levels of sTNFR1 and IL-10 were significantly higher than those in the CSF in AEPFS and PFS. The serum IL-10 and sTNFR1 levels in patients who did not experience a second seizure were significantly higher than those in patients who experienced a second seizure, which was characterized by clusters of complex partial seizures several days after the initial prolonged febrile seizure. Our results suggest that serum IL-6, IL-10, TNF-alpha, and CSF IL-6 are part of the regulatory system of cytokines in AEPFS.
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PMID:Serum and CSF levels of cytokines in acute encephalopathy following prolonged febrile seizures. 1759 22

In this review, the role of pro-inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory cytokine, IL-10, in the seizure activity development is analyzed. In recent years, there has been increasing evidence that the transformation of normal pattern of neuronal activity to paroxysmal one is associated with the increased production of these cytokines in the brain. However, the present results indicate that expressions of IL-1, TNF-alpha and IL-10 in the brain are associated with cell injury rather than with seizures per se. These findings suggest that, in response to seizures, these cytokines cause both neuroprotective or neurodegenerative effects and, as a consequence of these effects, the further facilitation or depression of seizure activity.
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PMID:[The role of cytokines in the seizure activity development in the brain]. 1806 92

Ischemic brain injury and epilepsy are common neurodegenerative diseases caused by excitotoxicity. Their pathogenesis includes microglial production of inflammatory cytokines. Our studies were designed to examine whether a growth compromised HSV-2 mutant (Delta RR) prevents excitotoxic injury through modulation of microglial responses by the anti-apoptotic HSV-2 protein ICP10PK. EOC2 and EOC20 microglial cells, which are differentially activated, were infected with Delta RR or the ICP10PK deleted virus (Delta PK) and examined for virus-induced neuroprotective activity. Both cell lines were non-permissive for virus growth, but expressed ICP10PK (Delta RR) or the PK deleted ICP10 protein p95 (Delta PK). Conditioned medium (CM) from Delta RR-, but not Delta PK-infected cells prevented N-methyl-D-aspartate (NMDA)-induced apoptosis of primary hippocampal cultures, as determined by TUNEL and caspase-3 activation (76.9 +/- 5.3% neuroprotection). Neuroprotection was associated with inhibition of TNF-alpha and RANTES and production of IL-10. The CM from Delta PK-infected EOC2 and EOC20 cells did not contain IL-10, but it contained TNF-alpha and RANTES. IL-10 neutralization significantly (p < 0.01) decreased, but did not abrogate, the neuroprotective activity of the CM from Delta RR-infected microglial cultures indicating that ICP10PK modulates the neuronal-microglial axis, also through induction of various microglial neuroprotective factors. Rats given Delta RR (but not Delta PK) by intranasal inoculation were protected from kainic acid (KA)-induced seizures and neuronal loss in the CA1 hippocampal fields. Protection was associated with a significant (p < 0.001) increase in the numbers of IL-10+ microglia (CD11b+) as compared to Delta PK-treated animals. Delta RR is a promising vaccination/therapy platform for neurodegeneration through its pro-survival functions in neurons as well as microglia modulation.
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PMID:DeltaRR vaccination protects from KA-induced seizures and neuronal loss through ICP10PK-mediated modulation of the neuronal-microglial axis. 1817 17


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