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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

For the past several years immunologists have been fascinated by a series of experiments showing that transforming growth factor beta (TGF beta) suppresses T- and B-lymphocyte growth as well as IgM and IgG production by B cells. Moreover, while exerting chemotactic activity on monocytes and inducing expression of interleukin-1 and interleukin-6 by these cells, TGF beta interferes with bacterially induced tumor necrosis factor alpha production, oxygen radical formation and the adhesiveness of granulocytes to endothelial cells. These mechanisms may provide the basis for the effect of TGF beta to prevent the microvascular changes associated with brain edema formation in bacterial meningitis. Given the potential of lymphocytes as well as macrophages to produce TGF beta 1, this cytokine may exert negative feedback signals on the immune response, provided the cytokine is processed from its latent form to the bioactive homodimer. Potent effects of TGF beta have been observed in experimental animals including the inhibition of the generation of virus-specific cytotoxic T cells and antiviral antibodies as well as the diminution of cellular infiltrates with decreased major histocompatibility complex class-II expression and CD8+ T cells in the tissue of virally infected animals. TGF beta may also be of importance in tumor immunology. By the production of bioactive TGF beta as detected in glioblastoma and acute T-cell leukemia, tumor cells may induce an immunodeficiency state and escape immune surveillance. In inflammation, monitoring of TGF beta in the tissue will bring light on the immune regulation in acute and chronic inflammatory diseases.
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PMID:Modulation of the immune response by transforming growth factor beta. 148 57

Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor beta (TGF-beta) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-beta on regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain edema formation during the early phase of experimental meningitis. Rats which were inoculated intracisternally with live pneumococci or with pneumococcal cell wall hydrolyzed by the M1 muramidase (PCW-M) developed an increase of rCBF and ICP within 4 h postintracisternal challenge. A single intraperitoneal injection of TGF-beta 2 but not of TGF-beta 2 vehicle-control prevented the changes of rCBF. Furthermore, TGF-beta 2 significantly reduced the increase of ICP in rats inoculated with PCW-M. Likewise, the elevation of brain water content after intracisternal injection of pneumococci or PCW-M was blocked by pretreatment of rats with TGF-beta 2. TGF-beta 1 exhibited similar inhibitory effects in PCW-M-injected rats. The beneficial effects of TGF-beta 2 on the initial phase after pneumococcal inoculation seem to be tumor necrosis factor alpha- (TNF-alpha) independent since (a) intracisternal or intraperitoneal injection of neutralizing anti-TNF-alpha antibodies did not significantly influence rCBF, ICP, and brain water content in PCW-M-induced meningitis; and (b) TNF-alpha was only occasionally detected at low levels in cerebrospinal fluid at 4 h after PCW-M application.
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PMID:Transforming growth factor beta 2 inhibits cerebrovascular changes and brain edema formation in the tumor necrosis factor alpha-independent early phase of experimental pneumococcal meningitis. 161 60

Recent developments in the pathogenesis, epidemiology and therapy of bacterial meningitis are presented. The importance of interleukin-1 beta, tumor necrosis factor alpha, and prostaglandins as generators of inflammation within the central nervous system in animals and children is described. The role of mediators of inflammation such as dexamethasone in the experimental meningitis model and in clinical studies is reviewed. The optimal duration of therapy and the role of cephalosporins in bacterial meningitis are discussed.
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PMID:[Bacterial meningitis]. 166 35

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

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

Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function. Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model. Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits. When pentoxifylline was given 1 h after H. influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals. Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H. influenzae meningitis. In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined. Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals. We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H. influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.
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PMID:Pentoxifylline modulates meningeal inflammation in experimental bacterial meningitis. 236 Aug 22

Since interleukin-10 (IL-10) controls the production of tumor necrosis factor alpha (TNF-alpha) and this latter cytokine has a deleterious effect on neuronal cells, we determined the levels of both cytokines in cerebrospinal fluid (CSF) from children with bacterial meningitis. High levels of IL-10 (1,164 pg/mL) and TNF-alpha (3,158 pg/mL) were detected in CSF from 10 children with meningitis, but these cytokines were not detectable in CSF from 12 controls. In vitro neutralization of IL-10 demonstrated that endogenously formed IL-10 is important for limiting the production of TNF-alpha by leukocytes. We assume that IL-10 in CSF will decrease the inflammatory reaction associated with meningitis and will result in the development of fewer sequelae because of its inhibitory effect on the production of TNF-alpha.
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PMID:High levels of interleukin 10 and tumor necrosis factor alpha in cerebrospinal fluid during the onset of bacterial meningitis. 872 71

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.
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PMID:Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis. 903 91

Levels of interleukin-6 and tumor necrosis factor alpha were measured in cerebrospinal fluids from patients with meningitis. Interleukin-6 was increased in aseptic and bacterial meningitis, whereas tumor necrosis factor alpha was increased only in bacterial meningitis. We concluded that measurement of cytokines in cerebrospinal fluid may be useful for the rapid diagnosis of meningitis.
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PMID:Clinical significance of cytokine measurement for detection of meningitis. 932 30


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