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

Sixty-five cerebrospinal fluid (CSF) samples from 54 infants and children with bacterial meningitis were analyzed for the presence of interferon (IFN)-alpha with a biologic assay. Of the 65 samples, 3 were positive (2-4 IU/mL) and only 1 of 56 collected early was at 4 IU/mL. These results suggest that some subtypes of IFN-alpha already reported as present in viral infections of the central nervous system are not detected in bacterial meningitis by our IFN assay. This difference may be helpful in differentiating bacterial from viral infections and also in evaluating the quality of the virologic investigation; moreover, the rarity of IFN-gamma in CSF in bacterial meningitis needs further investigation to understand its role in the pathogenesis of the disease.
 ...
PMID:Absence of intrathecal synthesis of some interferon-alpha subtypes in bacterial meningitis. 150 Jul 54

An easy, reproducible and semi-quantitative, non-radioactive method for the analysis of mRNA expression for various cytokines, (i.e., Interleukin (IL)-1 beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, lymphotoxin (LT), transforming growth factor (TGF)-beta, interferon (IFN)-gamma and endothelin-1 (ET-1)) in cells from cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) has been established. By means of polymerase chain reaction primers that cover a splice junction, amplification of contaminating DNA was omitted. Densitometric scanning of ethidium bromide-stained agarose gels proved to be very sensitive for semiquantitative analysis of PCR products. Serial tenfold dilutions of cDNA revealed a log-linear regression from 10(6) to 10(2) cells under optimal cycle conditions. The intra- and inter-assay variability of the method was below 10%. With this assay, the cytokine expression pattern of as few as 10(4) mononuclear cells from blood or CSF was determined. This method made it possible to detect differences in the cytokine gene expression pattern of mononuclear cells from patients with different neurological diseases. CSF cells from 43 patients with various neurological diseases were analyzed. TNF-alpha, LT, and IL-1 mRNA were prominent in the CSF cells of most patients with bacterial meningitis. TNF-alpha, LT, IFN-gamma and IL-6 mRNAs were detected in patients with active multiple sclerosis, whereas TNF-alpha, IL-6, and endothelin-1 mRNA expression was found frequently in patients with HIV encephalitis. Pro-inflammatory cytokines were rarely detected in CSF cells from patients with non-inflammatory diseases of the central nervous system. In blood mononuclear cells from patients with multiple sclerosis, TNF-alpha mRNA expression was associated with disease activity. The sensitivity, specificity, velocity and reliability of this assay considerably facilitates the analysis of cytokine production in mononuclear cells even in conditions where only a limited number of cells is available for analysis.
 ...
PMID:Semi-quantitative analysis of cytokine gene expression in blood and cerebrospinal fluid cells by reverse transcriptase polymerase chain reaction. 778

Interferon (IFN)-gamma was analysed immunologically in cerebrospinal fluid (CSF) sampled in the acute phase from 27 patients (15-66 years) with viral meningitis and from 18 patients (0.5-90 years) with bacterial meningitis. Increased CSF concentrations were observed in 19/27 viral and in 13/18 bacterial cases. CSF-IFN-gamma did not distinguish between viral and bacterial meningitis. Five of 8 patients with meningitis due to herpes simplex virus type 2 (HSV-2) had CSF-IFN-gamma levels above the highest found in enteroviral meningitis. Thus, a markedly increased CSF-IFN-gamma value in patients with suspected viral meningitis ought to indicate HSV-2 etiology. The patients with Streptococcus pneumoniae meningitis (6 adults and 1 child) had significantly higher levels than the 7 children with Haemophilus influenzae meningitis. This may indicate that S. pneumoniae induces more IFN-gamma secretion than H. influenzae, and/or that during meningitis, adults are more apt to react with IFN-gamma production, than are children.
 ...
PMID:Interferon-gamma in cerebrospinal fluid from patients with viral and bacterial meningitis. 803 69

Neopterin is synthesized mainly by monocytes/macrophages and is considered to be a marker for activation of the cellular immune system. In patients with bacterial or aseptic meningitis, elevated neopterin levels in cerebrospinal fluid (CSF) have been demonstrated. We studied the time courses of CSF and serum neopterin in children with meningitis. The CSF neopterin levels on admission were significantly higher in patients with bacterial meningitis (82.4 +/- 37.0 nmol/L) than in those with aseptic meningitis (32.3 +/- 22.1 nmol/L) or in those with non-pleocytotic CSF (6.9 +/- 4.4 nmol/L). The CSF neopterin levels in the patients with bacterial meningitis were remarkably increased (234.5 +/- 100.2 nmol/L) one day after admission, but the serum neopterin levels were not increased. There was no correlation between CSF neopterin levels and CSF cell count or CSF protein, nor between serum neopterin levels and serum C-reactive protein or peripheral leukocyte count. But the CSF neopterin levels one day after admission were related to the period of positive serum C-reactive protein. CSF neopterin levels in patients with bacterial meningitis were increased one day after admission. The levels in two patients with high levels of CSF IFN-gamma and TNF-alpha were remarkably increased. All patients with bacterial meningitis had received treatment with antibiotics and dexamethasone. It has been reported that TNF-alpha enhances the effect of IFN-gamma for neopterin release by macrophages in vitro and that dexamethasone has the same effect on IFN-gamma as TNF-alpha. The present study suggests that elevation of CSF neopterin in bacterial meningitis results from monocytes/macrophages costimulated with IFN-gamma, TNF-alpha and dexamethasone used in treatment.
 ...
PMID:[Changes of neopterin in cerebrospinal fluid and serum in children with meningitis]. 857 53

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.
 ...
PMID:Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis. 903 91

Intraperitoneal inoculation of Haemophilus influenzae type b (Hib) to 3-week-old Sprague-Dawley rats resulted in nonlethal meningitis with high levels of leukocytes in the cerebrospinal fluid (CSF) and positive bacterial culture. Using in situ hybridization, levels of cytokine mRNA-expressing cells were determined in the brain, CSF, and spleen from Hib-inoculated and uninfected control rats. IFN-gamma, IL-1 beta, IL-4, IL-6, IL-10, IL-12, and TNF-alpha mRNA levels were elevated at 12 hr postinoculation (pi) in spleen and CSF. At this time point, strong expression of IL-6 and TGF-beta was detected in the brain, and also of IL-10 at 48 hr while IFN-gamma and IL-12 were expressed at very low levels throughout the observation time. Delayed cytokine induction occurred in CSF compared to spleen and brain. TGF-beta was high in CSF at 48 hr, and some elevation of IL-1 beta, IL-6, IL-10, TNF-alpha, IFN-gamma, and IL-12 was evident at 72 hr pi. This may suggest measures that promote production of TGF-beta and/or IL-10 should be evaluated in treatment of bacterial meningitis.
 ...
PMID:Cytokine mRNA profiles during the course of experimental Haemophilus influenzae bacterial meningitis. 940 Jun 23

We have previously shown that immunoglobulin A1 (IgA1) protease, an exoenzyme of pathogenic neisseriae, can trigger the release of proinflammatory cytokines from human monocytic subpopulations. Here, we demonstrate a dose-dependent T-cell response to recombinant gonococcal IgA1 protease (strain MS11) in healthy human blood donors. This response was delayed in comparison to the immune response against tetanus toxoid. Stimulation with IgA1 protease led to the activation of CD4(+) and CD8(+) T cells, as well as CD19(+) B cells and CD56(+) NK cells, indicated by de novo expression of CD69. Only CD4(+) T cells proliferated and stained positive for intracellular gamma interferon (IFN-gamma). Both proliferation and IFN-gamma production were dependent on antigen presentation via major histocompatibility complex class II. Peripheral blood mononuclear cells stimulated with IgA1 protease produce IFN-gamma and tumor necrosis factor alpha but no, or very low amounts of, interleukin-10 (IL-10) or IL-4, indicating a Th1-based proinflammatory immune response. These findings support the significance of IgA1 protease as a virulence determinant of bacterial meningitis and its function as a dominant proinflammatory T-cell antigen.
 ...
PMID:Neisserial immunoglobulin A1 protease induces specific T-cell responses in humans. 1174 99

Myeloid (CD11c+) dendritic cells (DC) are present in cerebrospinal fluid (CSF), as well as in the meninges and choroid plexus. Functional studies of these DC are hindered or impossible. To obviate this problem, we investigated the effects of CSF supernatants from patients with non-inflammatory neurological diseases (NIND), multiple sclerosis (MS), bacterial meningitis (BM) and Lyme meningoencephalitis (LM) on immature monocyte-derived DC (moDC) from healthy donors. CSF supernatants caused maturation of moDC (MS > LM > NIND > BM), as reflected by a decrease in CD1a, and an increase in HLA-DR, CD80 and CD86 expression. The maturation effect of MS CSF and LM CSF could be blocked by anti-TNF-alpha MoAb or recombinant human IL-10. moDC cultured with BM CSF either remained immature or turned into CD14+ macrophage-like cells and were relatively inefficient at inducing T cell responses in vitro. In contrast, moDC cultured with LM CSF induced strong Th1 responses. Both BM CSF and LM CSF contained IFN-gamma, a cytokine that augments IL-12 production by moDC and hence should confer an ability to induce a Th1 response. However, BM CSF also contained high levels of IL-10, which could antagonize the effects of IFN-gamma on moDC. moDC cultured with MS CSF induced a higher production of IFN-gamma from T cells compared to moDC cultured with NIND CSF or BM CSF. In summary, soluble factors present in the CSF may influence the phenotype and functions of meningeal, choroid plexus and CSF DC which, in turn, may have an impact on the character of intrathecal T cell responses.
 ...
PMID:Cerebrospinal fluid affects phenotype and functions of myeloid dendritic cells. 1198 31

The involvement of the choroid plexus in host defense during bacterial meningitis is unclear. Aiming to elucidate possible antibacterial mechanisms, we stimulated primary porcine choroid plexus epithelial cells (pCPEC) with proinflammatory cytokines and challenged them with various Streptococcus suis strains. In the supernatant of gamma interferon (IFN-gamma)-stimulated pCPEC, streptococcal growth was markedly suppressed. Costimulation with tumor necrosis factor alpha enhanced this bacteriostatic effect, while supplementation of L-tryptophan completely eliminated it. We also demonstrate that an activation of indoleamine 2,3-dioxygenase in the pCPEC seems to be responsible for the IFN-gamma-induced bacteriostasis. This supports the hypothesis of an active role of the choroid plexus in host defense against bacterial meningitis.
 ...
PMID:Porcine choroid plexus epithelial cells induce Streptococcus suis bacteriostasis in vitro. 1510 28

We investigated whether monocyte-derived dendritic cells (MDDCs) generated in vitro from bacteria-infected MS patients modified autoreactive T cells activation patterns. T cell clones (TCCs) stimulated with MDDCs from infected MS patients responded with maximal proliferation, inducing IL-12, IL-17 and IFN-gamma secretion, at concentrations significantly lower than after incubation with MDDCs isolated from uninfected individuals and bacterial meningitis (BM) patients. Moreover, infected MDDCs promoted TCCs survival, and secreted more IL-12, IL-18, and IL-23. Finally, MDDCs from infected MS subjects showed higher expression of myeloid differentiation factor 88 (MyD88), as well as of HLA-DR, CD1a, CD80, CD86, CD273, CD40, CD83 and CCR7 when compared to MDDCs from uninfected MS individuals, and BM patients. Thus, activation of the innate immune system by microbial products in MS patients affects the generation MDDCs and their ability to modify autoreactive T cell activation patterns, which may be linked to MS relapse induction during bacterial infections.
 ...
PMID:Monocyte-derived dendritic cells in multiple sclerosis: the effect of bacterial infection. 1793 16


1 2 Next >>