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) plays a central role in the immune system, partly by stimulating the production of interleukin-2 (IL-2) and other cytokines by lymphocytes. In preclinical studies, recombinant interleukin-1 (rIL-1 beta) has shown antitumor activity. We conducted a phase II trial to evaluate the efficacy of rIL-1 in metastatic renal cell carcinoma (RCC). rIL-1 beta was given at a dose of 50 ng/kg i.v. daily for 5 days on a 28-day schedule. Nineteen patients were registered; 16 completed two cycles and were evaluable for response. There were no complete or partial responses to treatment. Toxicity was generally mild and typically involved grades I and II fever, rigors, hypotension, and weight gain. Severe neurologic toxicity was seen in two patients, grade IV seizures were seen in one, and grade III somnolence was seen in another. Analysis of soluble IL-2 receptor (sIL-2r) levels revealed an increase from a mean pretreatment level of 4,567 pg/ml to a mean of 6,124 pg/ml posttreatment (p < 0.001). The mean pretreatment IL-6 level was 51 pg/ml, increased to 84 pg/ml posttreatment (p < 0.05). Patients with bulky disease had higher sIL-2r levels, and patients with tumor fevers had higher IL-6 and sIL-2r levels than patients without fever did. A neutrophilic leukocytosis and a mild thrombocytosis were observed in response to rIL-1 beta administration. We conclude that rIL-1 beta in this dose and schedule is inactive in metastatic RCC.
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PMID:Phase II trial of recombinant interleukin-1 beta in patients with metastatic renal cell carcinoma. 783 20

There has been a growing body of evidence suggesting that CD4+ Th1/Th2 cell responses participate in pathologic and immunologic processes in infectious disease. Bacterial meningitis is a fatal disease of children and is associated with a spectrum of clinical syndromes. This study provides evidence of CD4+ enhanced interleukin (IL)-4 and IL-6 but decreased IL-2 and interferon-gamma (IFN-gamma) production, the induction of characteristic Th2 cell response cytokines in bacterial meningitis, which may play an important role in disease mechanism. Additionally, monocyte-induced enhanced IL-6, IL-8, and tumor necrosis factor-alpha production may be associated with distinct clinical features such as fever, seizures, and neurological sequelae. A striking finding was also the highly deficient monocyte-induced granulocyte-macrophage colony-stimulating factor production. Of particular interest, the CD(8+)-enhanced IFN-gamma production may be required for the cytolytic activity or protective response to be maintained in this disease. Taken together, these data reveal that monocytes and CD4+ (Th2) and CD8+ subsets produce distinct cytokines in bacterial meningitis, which may exert an immunoregulatory and immunopathologic effect and thus mediate some of the clinical manifestations of the disease.
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PMID:CD4+ Th2 cell response cytokine production in bacterial meningitis. 857 20

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

A 9-year-old female was admitted to our hospital due to a generalized seizure and consciousness disturbance. The patient had a fever and rash four days before admission, but she had no respiratory symptoms. The seizure and consciousness disturbance was prolonged and intractable. We diagnosed the patient as having encephalitis because of the increase in the cell count in the cerebrospinal fluid (CSF) and a diffuse slow EEG wave. The computed tomography of the head was normal. The causative agent was identified as Mycoplasma pneumoniae because of the increase of antibodies, and the detection of a specific DNA with a polymerase chain reaction. The interleukin (IL)-6 level of CSF was high (384 pg/ml). In spite of intensive treatment she had severe neurological sequelae. The invasion of Mycoplasma pneumoniae to the central nervous system appeared to have a role in the development of encephalitis in the patient. We speculated that there is a possible relationship between the IL-6 levels of CSF and clinical severity of encephalitis.
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PMID:[A case of encephalitis due to Mycoplasma pneumoniae: detection of specific DNA from cerebrospinal fluid and elevation of interleukin-6]. 974 29

The purpose of this review is to discuss ATF3, a member of the ATF/CREB family of transcription factors, and its roles in stress responses. In the introduction, we briefly describe the ATF/CREB family, which contains more than 10 proteins with the basic region-leucine zipper (bZip) DNA binding domain. We summarize their DNA binding and heterodimer formation with other bZip proteins, and discuss the nomenclature of these proteins. Over the years, identical or homologous cDNA clones have been isolated by different laboratories and given different names. We group these proteins into subgroups according to their amino acid similarity; we also list the alternative names for each member, and clarify some potential confusion in the nomenclature of this family of proteins. We then focus on ATF3 and its potential roles in stress responses. We review the evidence that the mRNA level of ATF3 greatly increases when the cells are exposed to stress signals. In animal experiments, the signals include ischemia, ischemia coupled with reperfusion, wounding, axotomy, toxicity, and seizure; in cultured cells, the signals include serum factors, cytokines, genotoxic agents, cell death-inducing agents, and the adenoviral protein E1A. Despite the overwhelming evidence for its induction by stress signals, not much else is known about ATF3. Preliminary results suggest that the JNK/SAPK pathway is involved in the induction of ATF3 by stress signals; in addition, IL-6 and p53 have been demonstrated to be required for the induction of ATF3 under certain conditions. The consequences of inducing ATF3 during stress responses are not clear. Transient transfection and in vitro transcription assays indicate that ATF3 represses transcription as a homodimer; however, ATF3 can activate transcription when coexpressed with its heterodimeric partners or other proteins. Therefore, it is possible that, when induced during stress responses, ATF3 activates some target genes but represses others, depending on the promoter context and cellular context. Even less is understood about the physiological significance of inducing ATF3. We will discuss our preliminary results and some reports by other investigators in this regard.
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PMID:ATF3 and stress responses. 1044 Feb 33

Parenteral injection of endotoxin has been used as a model to examine the role of pro-inflammatory cytokines in the centrally controlled responses to Gram-negative bacterial infection. However, the events that occur following mucosal exposure to live bacteria have received little attention. In this study, we have used a murine model to demonstrate that respiratory infection with Bordetella pertussis, which is associated with a number of systemic complications including fever, seizure and encephalopathy in children, resulted in persistent expression of mRNA transcripts for IL-1beta and TNFalpha and transient expression of IL-6 in the hippocampus and hypothalamus. These changes correlated with elevated levels of cytokine protein in the same brain areas. The results demonstrate that infection at a mucosal surface can result in the induction of pro-inflammatory cytokine production in the brain and suggest that these locally synthesized mediators may contribute to the centrally controlled clinical manifestations of B. pertussis infection.
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PMID:Induction of inflammatory cytokines in the brain following respiratory infection with Bordetella pertussis. 1063 86

We have previously reported increased concentrations of interleukin (1L)-6 in CSF from patients with tonic-clonic seizures, where increased cytokine production most likely is a consequence of neuronal epileptic activity associated with seizures. The biological effects of IL-6 are mediated by other cytokines, which are studied here in addition to IL-6. The purpose of this study was to analyze levels of soluble cytokines from plasma and CSF from patients with newly developed tonic-clonic seizures. The concentrations of IL-6, IL-1 receptor antagonist (IL-1RA), IL-1beta, tumor necrosis factor (TNFalpha) and nerve growth factor (NGF) were measured from plasma and CSF from 22 patients with newly developed tonic-clonic seizures within 24 h from the seizure and 18 controls. The mean concentrations of IL-6 were significantly increased in CSF (P<0.001) and plasma (P<0.01) after tonic-clonic seizures, there was some indication of increased concentrations of IL-1RA and no significant change in NGF, IL-1beta or TNFalpha. Our study shows that cytokine network is activated in patients after recent tonic-clonic seizures. We provide evidence of intrathecal production of IL-6 associated with electrical seizure activity.
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PMID:Interleukin-6 and interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures. 1096 11

To investigate pathophysiologies of Mycoplasma pneumoniae infection from an immunological point of view, we measured the levels of interleukin-18 (IL-18) (originally designated gamma interferon [IFN-gamma]-inducing factor) in 19 serum samples from 10 patients with pneumonia without pleural effusion (ages 1 to 16 years), 3 serum and 13 pleural fluid samples from 11 patients with pleural effusions (ages 11 months to 15 years), and 18 serum and 27 cerebrospinal fluid samples from 24 patients with central nervous system complications (ages 1 to 15 years). IL-18 was measured by a commercially available enzyme-linked immunosorbent assay kit (MBL, Nagoya, Japan). In addition, the levels of tumor necrosis factor alpha, IFN-gamma, IL-6, IL-12, and KL-6 (a mucin-like glycoprotein expressed on type 2 pneumocytes) were measured in selected samples. The results concerning pleural effusions showed that elevated levels of IL-18 in pleural fluid, but not in serum, were solely associated with a sustained fibrotic change of the lung on chest roentgenography which might represent a pathological feature of intraluminal organization. All the pleural fluid samples with elevated levels of IL-18 were positive by PCR for M. pneumoniae DNA. There was no association between IL-18 and IFN-gamma levels in serum or in the pleural fluid. On the other hand, elevated levels of IL-18 in serum, but not in cerebrospinal fluid samples, were observed in the cases complicated by central nervous system involvement, including profound brain dysfunction with seizures. Our study demonstrated that M. pneumoniae can induce IL-18 and that the enhanced local production of IL-18 in the lung is closely associated with pulmonary disease manifestation.
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PMID:Close association between pulmonary disease manifestation in Mycoplasma pneumoniae infection and enhanced local production of interleukin-18 in the lung, independent of gamma interferon. 1106 97

We have previously shown that IL-6 protein levels are increased in cerebrospinal fluid in humans after recent tonic-clonic seizures with unchanged levels of IL-1beta and TNFalpha. Here we studied the expression of cytokines IL-6, LIF, IL-1beta and TNFalpha and cytokine receptors IL-6R, LIFR and Gp130 in the rat brain after kainic acid-induced status epilepticus using Northern blot analysis and in situ hybridization histochemistry. After seizures, IL-6 mRNA was induced in the hippocampus, cortex, amygdala and meninges, and IL-6R was up-regulated in the hippocampus. LIF was up-regulated in the hippocampus, cortex and meninges after seizures, and LIFR mRNA was induced in the hippocampus and cortex. Gp130 was constitutively expressed in the brain. After seizures, Gp130 transcription was rapidly induced in the meninges. In thalamus, cortex, amygdala and hippocampus Gp130 mRNA was induced in a delayed fashion. IL-1beta transcription was induced in the temporal lobe cortex and thalamus, and TNFalpha in the hippocampus. In general, the cytokine and their receptor mRNA levels were low in intact rat brain, but were induced by seizures. Since IL-6 and LIF transcripts were induced in the meninges after seizures, the protein products of these transcripts may be more readily released in cerebrospinal fluid after seizures. In addition, the activity of IL-6 and LIF signaling pathways may be influenced by increased expression of their receptors after seizures.
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PMID:Expression of cytokines and cytokine receptors in the rat brain after kainic acid-induced seizures. 1259 Nov 61

Mollaret's meningitis is a rare disease of unknown etiology, characterized by repeated aseptic meningitis with transient neurological symptoms and quick recovery. The patient, a 16-year-old boy, had episodes of acute encephalitis followed by complete recovery every year from the age of 13 to 16 years. The symptoms at onset were loss of consciousness, a generalized tonic clonic seizure and pyramidal signs. He was first admitted to our hospital at the age of 15 years. EEG in the early stage showed diffuse low-voltage rhythmic fast actvity. He recovered consciousness after a week. At the age of 16 years, he was admitted again because of high fever (39 degrees C). Soon after admission, he had generalized tonic-clonic seizure and was accompanied by alternating deep coma and delirium. Cerebrospinal fluid examination during early stage revealed mild leukocytic pleocytosis, elevation of protein and a high level of IL-6. although brain CT and MRI showed no abnormal findings. EEG showed intermittent, diffuse, middle-voltage, rhythmic fast activity. After 5 days, the neurological symptoms completely disappeared with EEG normalization. To our knowledge, this is the first report of rhythmic fast activity on EEG in Mollaret's meningitis. The clinical pictures of this case suggest a transient functional disorder of brainstem or cerebrum may occur in this condition.
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PMID:[Rhythmic fast activity on EEG in a patient with Mollaret's meningitis]. 1275 55


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