Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukemia inhibitory factor (LIF) has many biological actions which parallel those of IL-1, IL-6 and tumor necrosis factor-alpha, but its role in the pathogenesis of human disease is unknown. A specific radioreceptor competition assay capable of detecting LIF at concentrations above 1 ng/ml (45 pM) was developed. To identify disease states in which LIF might be involved, a cross-sectional survey of serum and body fluids from approximately 1,500 subjects with a variety of diseases was performed using the LIF radioreceptor competition assay. Serum LIF concentrations were transiently elevated (2-200 ng/ml) in six subjects with meningococcal or Gram-negative septic shock, and in a subject with idiopathic fulminant hepatic failure. Moderately elevated LIF concentrations (> 10 ng/ml) were detected in cerebrospinal fluid from subjects with bacterial meningitis, in effusions associated with pneumonia and peritonitis, and in amniotic fluid from a woman with chorioamnionitis. Low LIF concentrations (1-10 ng/ml) were present in synovial fluid from subjects with inflammatory arthritis, amniotic fluid from women in labor, and some reactive, chronic inflammatory and malignant effusions and cyst fluids, but rarely in transudates. These initial findings suggest that LIF might be involved in the pathogenesis of inflammation and septic shock.
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PMID:Leukemia inhibitory factor levels are elevated in septic shock and various inflammatory body fluids. 143 Feb 24

Cytokines have been implicated in the pathogenesis of gram-negative bacterial meningitis. The effects of pentoxifylline and dexamethasone on the release of tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6 from primary murine microglial cell cultures were explored using bioassays. When added concomitantly with lipopolysaccharide, pentoxifylline blocked the release of TNF and IL-1 but not IL-6, while dexamethasone inhibited the release of TNF and IL-6. After a 2-h exposure of microglia to lipopolysaccharide, pentoxifylline but not dexamethasone still inhibited the release of TNF. Release of TNF was enhanced 20-fold by priming of the microglia with interferon-gamma; only pentoxifylline blocked the priming effect of interferon-gamma on TNF release. These results demonstrate that pentoxifylline and dexamethasone differentially regulate the release of cytokines in microglial cell cultures and provide potential insight into their role in the treatment of gram-negative bacterial meningitis.
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PMID:Cytokine release from microglia: differential inhibition by pentoxifylline and dexamethasone. 152 22

The levels of interleukin-1 beta, IL-1 receptor antagonist and tumor necrosis factor-alpha (TNF-alpha) were analyzed in 19 cases of tuberculous, 14 cases of viral, and 22 cases of acute bacterial meningitis, and in 18 control subjects. 20 patients (91%) with acute bacterial and 8 (42%) with tuberculous meningitis had detectable amounts of TNF-alpha in the initial cerebrospinal fluid (CSF) sample (mean 1044 +/- 131 pg/ml, range 95-1950, and mean 61 +/- 23 pg/ml, range 25-300, respectively), whereas TNF-alpha was not detectable in any of the patients with viral meningitis, or in any of the control subjects. IL-1 beta levels were 767 +/- 110 pg/ml (185-2000) in acute bacterial, 345 +/- 63 pg/ml (50-670) in tuberculous, 257 +/- 70 pg/ml (20-700) in viral meningitis, and 37 +/- 4 pg/ml (10-68) in control subjects. Il-1 receptor antagonist concentrations were significantly elevated in all meningitis groups, without significant differences between the groups. Il-1 receptor antagonist levels were 2487 +/- 62 pg/ml (2250-2950) in acute bacterial, 2216 +/- 82 pg/ml (1350-2550) in tuberculous and 1985 +/- 92 pg/ml (650-2500) in viral meningitis, and 154 +/- 26 pg/ml (20-245) in control CSF samples. A positive correlation was found between TNF and IL-1 beta levels (p < 0.01), and TNF levels and conscious state (p < 0.05). The ratio of concentrations of IL-1 receptor antagonist to IL-1 beta was 3.2 in acute bacterial meningitis, 6.9 in tuberculous meningitis and 8.3 in viral meningitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid interleukin-1 beta/interleukin-1 receptor antagonist balance and tumor necrosis factor-alpha concentrations in tuberculous, viral and acute bacterial meningitis. 774 89

Interleukin-8 (IL-8) elaborated by monocytes and endothelial cells is a cytokine which is responsible for adhesion of leucocytes to vascular endothelium and migration of neutrophils into the cerebrospinal fluid (CSF) from the intravascular space. The inflammation in meningitis is elicited by the cytokine release from leucocytes which encounter micro-organisms in the arachnoid or subarachnoid space. In bacterial meningitis, tumour necrosis factor (TNF), IL-1 and IL-6 are produced vigorously, and initiate and augment the inflammation in the central nervous system. In this study, utilizing a quantitative immunometric sandwich enzyme immunoassay, the concentration of IL-8 was investigated in the CSF of patients with bacterial meningitis, patients with aseptic meningitis, and patients with gastroenteritis who served as controls. The IL-8 concentration was markedly higher in the CSF of patients with bacterial meningitis (224 +/- 2.57 pg/ml; mean +/- SD) than in the CSF of patients with aseptic meningitis (less than 30 pg/ml). The IL-8 level in the CSF of patients with aseptic meningitis did not differ from that in the CSF of the patients with gastroenteritis (less than 30 pg/ml). The augmented production of IL-8 in CSF may account for the inflammation in bacterial meningitis being more severe than that in aseptic meningitis.
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PMID:Augmented production of interleukin-8 in cerebrospinal fluid in bacterial meningitis. 826 63

Cytokines are involved in the host response to bacterial infections. In bacterial meningitis, intrathecal synthesis of TNF-alpha and IL-1 is likely to contribute to CNS injury by recruitment and activation of inflammatory cells with subsequent release of toxic factors, such as reactive oxygen intermediates and excitatory amino acids (glutamate), leading to neuronal cell death with neurologic sequelae. In rats with experimental meningitis, pretreatment with TGF-beta inhibits cerebrovascular changes and brain edema formation in the early, TNF-alpha-independent phase. Provided its local production in bacterial infection, TGF-beta may comprise a host factor interfering with immune pathologic events altering the integrity of the endothelial barrier.
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PMID:Immune-mediated injury in bacterial meningitis. 845 12

In experimental bacterial meningitis in rabbits, the inflammatory process is largely mediated by cytokines such as IL-1 and TNF-alpha. Since thalidomide has been shown to inhibit TNF-alpha production, experiments were carried out to determine whether the drug can modulate the inflammatory response to either lysates of H. influenzae (gram negative) or heat killed S. pneumoniae (gram positive) in rabbits. The introduction of a lysate of H. influenzae into the CSF of rabbits causes a very acute inflammatory response, as indicated by a rapid increase in TNF-alpha levels in the CSF and a concomitantly rapid leukocytosis. In contrast, the introduction of heat killed S. pneumoniae, induces a more indolent inflammatory response which also wanes more slowly. Thalidomide treatment reduces TNF-alpha production in both experimental systems, but has a greater effect on the more indolent gram positive inflammatory response in which peak TNF-alpha levels in the CSF are reduced by > 50%. Also, a sustained inhibition of leukocytosis is observed in the inflammatory response to heat-killed gram positive bacteria. In meningeal inflammation induced by the Gram negative lysate, treatment with thalidomide results in only a 29% inhibition of TNF-alpha release into the CSF. In contrast to the drug effect on TNF-alpha, thalidomide treatment does not significantly affect IL-1 levels in these models of rabbit bacterial meningitis.
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PMID:Effect of thalidomide on the inflammatory response in cerebrospinal fluid in experimental bacterial meningitis. 882 12

Tumour necrosis factor (TNF)-alpha, a strong immune mediator, is released within the brain during inflammatory diseases and contributes to immunological activation of glial cells. Here we report that, in astrocytes, TNF-alpha also affects the intracellular Ca2+ homeostasis and basic electrophysiological properties such as the membrane potential. Using the Ca2+ indicator dye fura-2 in a cell culture model, we found that TNF-alpha (10-1000 U ml-1), but not interleukin 1 or 6, induced a slow but more than two-fold increase of the intracellular Ca2+ concentration, which could be blocked by Co2+ (1.0 mM), verapamil (100 microM) or omission of external Ca2+. This intracellular Ca2+ increase was accompanied by a marked decrease of the membrane potential by 35 mV. CSF of patients with bacterial meningitis, known to contain large amounts of TNF-alpha, induced a similar depolarization of astrocytes, which was markedly reduced by a neutralizing anti-TNF-alpha antibody. We conclude that TNF-alpha induces an increase of intracellular Ca2+ and a depolarization in astrocytes with the consequence of disturbing voltage-dependent glial functions such as regulation of local ion concentrations and glutamate uptake. During inflammatory CNS diseases this immuno-electrical coupling may contribute to an impairment of neuronal function.
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PMID:Tumour necrosis factor-alpha increases intracellular Ca2+ and induces a depolarization in cultured astroglial cells. 901 6

Interleukin-1beta (IL-1beta) is considered an important mediator in the pathogenesis of septic shock or bacterial meningitis. Its activity is specifically modulated by IL-1 receptor antagonist (IL-1Ra) and IL-1 soluble receptor type II (IL-1sRII). We now describe the time-course of IL-1beta and these modulating agents in 59 patients with acute meningococcal infections, the prototype human disease of acute endotoxin exposure. Plasma IL-1beta was increased only in severe shock and normalized within 12 to 24 hours, indicating that patients were admitted in an early stage of cytokine activation. Increased IL-1beta values in cerebrospinal fluid (CSF) were confined to patients with meningitis. Plasma IL-1Ra was elevated in both shock and nonshock patients, extremely high values being measured in severe shock. High concentrations of IL-1Ra in CSF were found in meningitis. Plasma IL-1Ra peaked shortly after IL-1beta and decreased steeply in 1 to 2 days, followed by sustained moderately elevated levels in shock patients. Interestingly, IL-1sRII showed a completely different pattern. At admission, both nonshock and shock patients manifested a similar moderate increase of plasma IL-1sRII. However, during recovery plasma IL-1sRII further increased reaching maximal concentrations 3 to 5 days after admission, 1 to 2 days after normalization of IL-1Ra. In shock patients this increase was more prominent than in nonshock patients. It is hypothesized that this increase in plasma IL-1sRII can be explained by a synergistic effect of dexamethasone and endotoxin. A second interesting observation was that, unlike the pattern in plasma, IL-1sRII levels in CSF paralleled those of IL-1beta and IL-1Ra. This suggests different modulation of IL-1beta activity in the subarachnoid space and the plasma compartment. We conclude that: (1) During the early stage of meningococcal infections IL-1Ra modulates IL-1 activity, whereas during recovery IL-1sRII may be more important. (2) Modulation in CSF and in the plasma compartment are differentially regulated.
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PMID:The pattern of interleukin-1beta (IL-1beta) and its modulating agents IL-1 receptor antagonist and IL-1 soluble receptor type II in acute meningococcal infections. 924 41

In bacterial meningitis, chemokines lead to recruitment of polymorphonuclear leucocytes (PMN) into the CNS. At the site of infection in the subarachnoid space, PMN release reactive oxygen species, reactive nitrogen intermediates (RNI) and interleukin-1beta (IL-1beta). Although these immune factors assist in clearance of bacteria, they also result in neuronal injury associated with meningitis. Transforming growth factor beta (TGFbeta) is a potent deactivator of PMN and macrophages since TGFbeta suppresses the production of ROI, RNI and IL-1. Here, we report that the deletion of the TGFbeta receptor II gene in PMN enhances PMN recruitment into the CNS of mice with Streptococcus pneumoniae meningitis. This was associated with more efficient clearance of bacteria, and almost complete prevention of intracerebral necrotizing vasculitis. Differences in PMN in the CNS of infected control mice and mice lacking TGFbeta receptor II were not explained by altered expression of chemokines acting on PMN. Instead, TGFbeta was found to impair the expression of L (leucocyte)-selectin on PMN from control mice but not from mice lacking TGFbeta receptor II. L-selectin is known to be essential for PMN recruitment in bacterial meningitis. We conclude that defective TGFbeta signalling in PMN is beneficial in bacterial meningitis by ameliorating migration of PMN and bacterial clearance.
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PMID:TGFbeta receptor II gene deletion in leucocytes prevents cerebral vasculitis in bacterial meningitis. 1689 35

In response to tissue injury or infection, the peripheral tissue macrophage induces an inflammatory response through the release of IL-1beta (interleukin-1beta) and TNFalpha (tumour necrosis factor alpha). These cytokines stimulate macrophages and endothelial cells to express chemokines and adhesion molecules that attract leucocytes into the peripheral site of injury or infection. The aims of the present review are to (i) discuss the relevance of brain (peri)vascular cells and compartments to bacterial meningitis, HIV-1-associated dementia, multiple sclerosis, ischaemic and traumatic brain injury, and Alzheimer's disease, and (ii) to provide an overview of the production and action of pro-inflammatory cytokines by (peri)vascular cells in these pathologies of the CNS (central nervous system). The brain (peri)vascular compartments are highly relevant to pathologies affecting the CNS, as infections are almost exclusively blood-borne. Insults disrupt blood and energy flow to neurons, and active brain-to-blood transport mechanisms, which are the bottleneck in the clearance of unwanted molecules from the brain. Perivascular macrophages are the most reactive cell type and produce IL-1beta and TNFalpha after infection or injury to the CNS. The main cellular target for IL-1beta and TNFalpha produced in the brain (peri)vascular compartment is the endothelium, where these cytokines induce the expression of adhesion molecules and promote leucocyte infiltration. Whether this and other effects of IL-1 and TNF in the brain (peri)vascular compartments are detrimental or beneficial in neuropathology remains to be shown and requires a clear understanding of the role of these cytokines in both damaging and repair processes in the CNS.
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PMID:(Peri)vascular production and action of pro-inflammatory cytokines in brain pathology. 1713 37


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