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Query: UMLS:C0085437 (bacterial meningitis)
 4,038 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to understand the role of TNF in the central nervous system (CNS) pathophysiologic events associated with bacterial meningitis, we examined the effect of intravenous vs. intracisternal administration of TNF alpha on penetration of circulating 125I-labeled albumin into cerebrospinal fluid (CSF) and CSF white blood cell (WBC) counts in rats. Intracisternal administration of tumor necrosis factor alpha (TNF-alpha) resulted in dose- and time-dependent alterations of the CSF penetration and CSF WBCs, while intravenous administration of TNF-alpha did not induce any changes. These changes by intracisternal TNF were abolished by heat treatment of TNF or coadministration of MAb to TNF-alpha. Mab to TNF-alpha also significantly reduced the CSF penetration of circulating albumin in experimental hematogenous Haemophilus influenzae type b meningitis in infant rats but this salutary effect required both intravenous and intracisternal administration. However, MAb to TNF-alpha failed to affect CSF pleocytosis in experimental hematogenous meningitis. These findings suggest that some of CNS pathophysiologic changes in bacterial meningitis may be a result of the local production of TNF but other host inflammatory responses may also participate in CNS inflammation in hematogenous bacterial meningitis.
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PMID:Modulation of blood-brain barrier permeability by tumor necrosis factor and antibody to tumor necrosis factor in the rat. 147 82

Brain damage after meningeal infection could result from impairment of cerebral endothelial cell functions and disruption of blood-brain barriers. Tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) produce many of their effects by acting on endothelial cells. This study correlates levels of TNF alpha and IL-1 beta in paired cerebrospinal fluid (CSF) and serum samples with the degree of blood-brain barrier damage, as manifested by CSF to serum albumin quotient, in 48 patients with bacterial meningitis and 66 controls. CSF levels of TNF alpha and IL-1 beta in bacterial meningitis were significantly higher than in controls. Intrathecal levels of TNF alpha, but not IL-1 beta, correlated with albumin quotient (P less than .001), with degree of blood-brain barrier disruption (P less than .001), and with disease severity and indices of meningeal inflammation. Sequential CSF samples demonstrated that IL-1 beta and TNF alpha disappear from the CSF within 24 h of antibiotic treatment. Data presented here suggest that TNF alpha is related to blood-brain barrier damage in bacterial meningitis and that its effect could be dissociated from that of IL-1 beta.
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PMID:Blood-brain barrier damage in patients with bacterial meningitis: association with tumor necrosis factor-alpha but not interleukin-1 beta. 163 6

In recent years the treatment of bacterial meningitis has been modified on the basis of a better understanding of its physiopathological mechanisms. It has been shown, for example, that the inflammatory reaction is the primary cause of brain damage in bacterial meningitis. Inflammation and consequent brain damage are greatest in the first hours of antibiotic treatment when rapid and massive bacteriolysis takes place. In effect, the bacterial components activate metabolic pathways and cellular elements leading to the release of inflammation mediators: cytokines (TNF, IL-I) neutrophil degranulation products, complement components and clotting factors. Initially these substances make the blood-fluid and blood-brain barriers permeable. The result is cerebral oedema, excessive fluid pressure, congestion of the cerebral blood vessels and finally endocranial hypertension, reduced cerebral flow, cerebral hypoxia and brain damage. This sequence of events can be stopped by a multifactorial therapy that is not only aetiological (antibiotic) but also treats the inflammation, oedema (Dexamethasone, Mannitol) and symptoms. In this study 129 patients with non-tubercular bacterial meningitis were treated as described. All patients were administered Ceftriaxone (100 mg/kg per diem) Dexamethasone (0.2-0.3 mg/kg/per diem), Mannitol, fluid restriction and--where necessary--intensive symptomatic therapy (against shock, convulsions, fever). Both the antibiotic and the corticosteroid were also administered intrathecally at the time of the first lumbar puncture at intake. Of these 129 patients, 7 died very soon after admission as they had arrived in a moribund condition. Duration of therapy was 3-6 days in 90% of these cases. There were no recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rational basis of modern therapy of bacterial meningitis. Review of the literature and our clinical experience of 122 pediatric cases. 180 76

In bacterial meningitis, LPS induces production in cerebrospinal fluid of the cytokines IL-1 beta and tumor necrosis factor alpha (TNF alpha), which are the principle mediators of meningeal inflammation. IL-1 beta and TNF alpha induce fever, and elevated temperature may affect cytokine expression. Dexamethasone treatment improves outcome in bacterial meningitis possibly by inhibiting IL-1 beta and TNF alpha. In this report, the effects of elevated temperature and dexamethasone on LPS-stimulated IL-1 beta and TNF alpha mRNA gene expression and protein synthesis were studied in human astrocytoma cell lines and primary cultures of human fetal astrocytes. Cells cultured at 40 degrees C exhibited smaller peaks of IL-1 beta and TNF alpha transcription and protein synthesis compared with cells cultured at 37 degrees C. The addition of dexamethasone before, during, or after exposure of the cells to LPS resulted in temperature-dependent inhibition of IL-1 beta transcription and protein synthesis. The most extensive inhibition occurred in pretreated cells cultured at 37 degrees C. Cotreatment with LPS and dexamethasone also inhibited TNF alpha mRNA transcription at both temperatures. The effects of another antiinflammatory agent, indomethacin, on LPS induction of IL-1 beta and TNF alpha mRNA were temperature and cell line dependent. These findings provide a possible explanation for the efficacy of dexamethasone treatment of bacterial meningitis and support the proposal that fever may be beneficial to the host in this disease.
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PMID:Temperature-dependent modulation of lipopolysaccharide-induced interleukin-1 beta and tumor necrosis factor alpha expression in cultured human astroglial cells by dexamethasone and indomethacin. 202 38

Although antibiotics have reduced mortality, the most recent clinical trials in sepsis and meningitis have been directed at the host inflammatory response in an attempt to improve outcome. Endotoxin, cell wall constituents and toxins are potent inducers of small molecular weight proteins (cytokines) from a variety of host cells. Several lines of investigation have implicated tumor necrosis factor-alpha (TNF-alpha) as a cytokine mediator of sepsis and septic shock. A recent study has been able to measure plasma TNF-alpha concentrations in patients with meningococcemia and demonstrated a correlation with prognostic groups related to mortality. Therefore, TNF-alpha, probably through its effects on other mediators, has an effect in sepsis. New speculation regarding morbidity in bacterial meningitis focuses on cytokine activity in the central nervous system. Cerebrospinal fluid (CSF) from experimental animals with meningitis contains increased amounts of interleukin-1 beta (IL-1 beta) and TNF alpha. These IL-1 beta levels correlated directly with duration of fever and neurological sequelae. Children with Haemophilus influenzae, type b meningitis treated with dexamethasone had significantly reduced levels of CSF IL-1 beta compared to placebo-treated controls.
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PMID:The immunology of sepsis and meningitis--cytokine biology. 209 Dec 57

Prostaglandins (PGs), interleukin 1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) are likely mediators of local inflammatory reactions. We measured PGE2, PGI2, IL-1 beta, and TNF concentrations in paired cerebrospinal fluid (CSF) samples (on admission, CSF1, and 18 to 30 hours later, CSF2) from 80 infants and children with bacterial meningitis. Forty patients received dexamethasone sodium (0.6 mg/kg per day in four intravenous doses) and 40 received an intravenous saline placebo. In CSF1, PGE2, PGI2, IL-1 beta, and TNF were detected in 90%, 56%, 98%, and 71% of specimens with mean (+/- SEM) concentrations of 462 +/- 65, 377 +/- 62, 1266 +/- 242, and 799 +/- 227 pg/mL, respectively. Concentrations of PGE2 correlated significantly with PGI2, IL-1 beta, TNF, and lactate and inversely correlated with glucose concentrations in the first CSF specimens. The PGE2, PGI2, IL-1 beta, and TNF were still detected in 40%, 18%, 97%, and 60%, respectively, of second CSF specimens obtained from placebo-treated patients. Compared with patients who had detectable PGI2 or TNF alpha concentrations in CSF2 specimens, those placebo-treated patients with no detectable PGI2 or TNF alpha activity in CSF2 had a lower incidence of neurological sequelae. Dexamethasone-treated patients had significantly lower PGE2, IL-1 beta, and lactate concentrations and higher glucose concentrations in CSF 18 to 30 hours later, shorter duration of fever, and a lower incidence of neurological sequelae than did placebo-treated patients.
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PMID:Cerebrospinal fluid prostaglandins, interleukin 1 beta, and tumor necrosis factor in bacterial meningitis. Clinical and laboratory correlations in placebo-treated and dexamethasone-treated patients. 211 86

In prospective studies, tumor necrosis factor (TNF alpha) was detected in cerebrospinal fluid (CSF) of 33 of 38 children with bacterial meningitis (BM) but in none of 15 with viral meningitis/encephalitis (P less than .001). BM CSF TNF alpha (less than 35 to greater than 25,500 pg/ml) correlated with CSF bacterial density (P less than .01), CSF protein (P less than .001), endotoxin (LPS) in gram-negative disease (P less than .01), and consecutive febrile hospital days (P less than .001); initial CSF TNF alpha greater than 1000 pg/ml was associated with seizures (P less than .05). Only 5 children with BM (13%) had detectable plasma TNF alpha activity on admission. A higher proportion who died had detectable plasma TNF alpha activity compared with survivors (3/4 vs. 2/34, P less than .005). Platelet-activating factor (PAF) in CSF was higher in 19 children with Haemophilus influenzae meningitis than in 17 controls (P less than .01) and correlated with bacterial density (P less than .01), CSF LPS (P less than .01), CSF TNF alpha levels (P less than .01), and the Herson-Todd severity score (P less than .01). Elevated CSF TNF alpha and PAF are often present in children with BM and are associated with seizures and severity of disease. Detectable CSF TNF alpha appears to distinguish BM from viral meningitis.
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PMID:Cerebrospinal fluid cachectin/tumor necrosis factor-alpha and platelet-activating factor concentrations and severity of bacterial meningitis in children. 201 66

Inflammatory response plays an important role in the pathogenesis of cerebral injury in bacterial meningitis. In this study, we evaluated the cytokine levels of interleukin 1-beta (IL1 beta), tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL6) in the cerebrospinal fluid (CSF), and determined their correlation with acute clinical complications and with changes in CSF biochemistry. Interleukin 6, TNF alpha and IL1 beta were present in 9/9, 3/9 and 4/9 patients, respectively. The CSFs with detectable TNF alpha or IL1 beta had higher levels of IL6 (p < 0.02), protein (NS) and lower glucose levels (p < 0.02), compared with those in which TNF alpha and IL1 beta were absent. Tumour necrosis factor alpha and IL1 beta levels also correlated with the presence of prolonged fever, fits, spasticity and death (logTNF alpha: r = 0.70, p < 0.05; logIL1 beta: r = 0.62, p = 0.08). The cytokine levels reflect the degree of inflammatory response and are positively correlated with the severity of acute clinical complications. Modulation of this inflammatory response in bacterial meningitis may improve its morbidity and mortality.
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PMID:Inflammatory response in bacterial meningitis: cytokine levels in the cerebrospinal fluid. 759 38

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

Among the important pathophysiologic alterations in the brain in bacterial meningitis are abnormalities of cerebral circulation and metabolism; however, the precise mechanisms by which these disturbances occur are not completely delineated. It has been recently recognized that cytokines are produced by tissues in the central nervous system in meningitis and play a critical role in the host inflammatory response. Because these mediators are involved in circulatory and metabolic disturbances in other tissues in sepsis, we investigated the role of tumor necrosis factor-alpha in the central nervous system in a rabbit model. We found that injection of recombinant human TNF into the cisterna magna in the rabbit led to an acute reduction in cerebral oxygen uptake and a more prolonged reduction in cerebral blood flow. This was accompanied by an increase in intracranial pressure and an increase in cerebrospinal fluid lactate. Reduction in oxygen uptake and increases in intracranial pressure and CSF lactate were blocked by pretreatment with L-NAME, an inhibitor of nitric oxide synthase. Reduction in cerebral blood flow was not affected by L-NAME treatment and was due to increased cerebrovascular resistance and reduced oxygen demand. These results suggest that TNF may be a critical mediator of changes in cerebral circulation and metabolism and that some of these changes occur via the nitric oxide pathway.
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PMID:Effect of recombinant human tumor necrosis factor-alpha on cerebral oxygen uptake, cerebrospinal fluid lactate, and cerebral blood flow in the rabbit: role of nitric oxide. 788 56


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