Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theiler's murine encephalomyelitis virus (TMEV) infection and relapsing-remitting experimental allergic encephalomyelitis (R-EAE) have been used to investigate the viral and autoimmune etiology of multiple sclerosis (MS), a possible Th1-type mediated disease. DNA immunization is a novel vaccination strategy in which few harmful effects have been reported. Bacterial DNA and oligodeoxynucleotides, which contain CpG motifs, have been reported to enhance immunostimulation. Our objectives were two-fold: first, to ascertain whether plasmid DNA, pCMV, which is widely used as a vector in DNA immunization studies, could exert immunostimulation in vitro; and second, to test if pCMV injection could modulate animal models for MS in vivo. We demonstrated that this bacterially derived DNA could induce interleukin (IL)-12, interferon (IFN)gamma, (Th1-promoting cytokines), and IL-6 production as well as activate NK cells. Following pCMV injections, SJL/J mice were infected with TMEV or challenged with encephalitogenic myelin proteolipid protein (PLP) peptides. pCMV injection exacerbated TMEV-induced demyelinating disease in a dose-dependent manner. Exacerbation of the disease did not correlate with the number of TMEV-antigen positive cells but did with an increase in anti-TMEV antibody. pCMV injection also enhanced R-EAE with increased IFNgamma and IL-6 responses. These results caution the use of DNA vaccination in MS patients and other possible Th1-mediated diseases.
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PMID:Exacerbation of viral and autoimmune animal models for multiple sclerosis by bacterial DNA. 1041 88

T cell-mediated inflammation is considered to play a key role in the pathogenic mechanisms sustaining multiple sclerosis (MS). Caspase-1, formerly designated IL-1beta-converting enzyme, is crucially involved in immune-mediated inflammation because of its pivotal role in regulating the cellular export of IL-1beta and IL-18. We studied the role of caspase-1 in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. Caspase-1 is transcriptionally induced during EAE, and its levels correlate with the clinical course and transcription rate of proinflammatory cytokines such as TNF-alpha, IL-1beta, IFN-gamma, and IL-6. A reduction of EAE incidence and severity is observed in caspase-1-deficient mice, depending on the immunogenicity and on the amount of the encephalitogenic myelin oligodendrocyte glycoprotein (MOG) peptide used. In caspase-1-deficient mice, reduced EAE incidence correlates with defective development of anti-MOG IFN-gamma-producing Th1 cells. Finally, pharmacological blockade of caspase-1 in Biozzi AB/H mice, immunized with spinal cord homogenate or MOG35-55 peptide, by the caspase-1-inhibitor Z-Val-Ala-dl -Asp-fluoromethylketone, significantly reduces EAE incidence in a preventive but not in a therapeutic protocol. These results indicate that caspase-1 plays an important role in the early stage of the immune-mediated inflammatory process leading to EAE, thus representing a possible therapeutic target in the acute phase of relapsing remitting MS.
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PMID:Caspase-1 regulates the inflammatory process leading to autoimmune demyelination. 1045 74

We investigated the role of IL-6 in myelin oligodendrocyte glycoprotein (MOG) peptide induced experimental autoimmune encephalomyelitis (EAE) using IL-6-deficient mice and found that IL-6-deficient mice were resistant to active induction of EAE, but that the treatment of those mice with IL-6 during the preclinical phase caused typical EAE. We also found that both wild-type and IL-6-deficient mice were resistant to passive transfer of EAE by lymphocytes from IL-6-deficient mice, but that passive transfer of lymphocytes from wild-type mice induced typical EAE in IL-6-deficient mice. Histological abnormalities of the central nervous system (CNS) in those IL-6-deficient mice with EAE were similar to those in wild-type mice with EAE. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed no difference in the production of inflammatory cytokines such as IL-1beta, IL-2, TNF-alpha, and IFN-gamma in the CNS of IL-6-deficient mice with EAE as compared to the CNS of wild-type mice with EAE. These results indicated that IL-6 might be an important factor in the induction phase, but might have little influence on the effector phase of EAE. We further estimated the production of cytokines in MOG-stimulated lymph node (LN) cells by enzyme-linked immunosorbent assay. Increased IL-4 and IL-10 production and reduced IL-2 and IFN-gamma production were observed in LN cells from IL-6-deficient mice as compared to LN cells from wild-type mice. These results suggested that a shift of T cell responses from Thl to Th2 might explain the resistance of IL-6-deficient mice to EAE. Taken together, IL-6 may play a crucial role in the induction phase of EAE by modulating Th1/Th2 balance.
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PMID:IL-6 plays a crucial role in the induction phase of myelin oligodendrocyte glucoprotein 35-55 induced experimental autoimmune encephalomyelitis. 1058 Aug 1

After primary immunization with myelin/oligodendrocyte glycoprotein, CD28(-/-) mice developed experimental autoimmune meningitis (EAM) rather than experimental autoimmune encephalomyelitis (EAE). Cytokine and chemokine production in EAE and EAM were compared to understand the differences in disease phenotype. T cells from the central nervous system lesions of mice with either EAE or EAM expressed intracellular TNF-alpha. Splenic T cells from mice with EAM produced TNF-alpha and IL-6 but no IL-2. Conversely, EAE-derived splenic T cells produced TNF-alpha and IL-2 but no IL-6. Altered T cell differentiation in EAM was not due to a Th1 to Th2 shift, because equivalent amounts of T cell IFN-gamma mRNA were produced in both diseases. Neutrophils also produced inflammatory mediators such as TNF-alpha and IL-6 in EAM. Autocrine production of MIP-2 mRNA was observed in neutrophils from mice with EAM but not EAE. Therefore, distinct patterns of cytokines and chemokines distinguish EAE and EAM.
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PMID:Differential cytokine and chemokine production characterizes experimental autoimmune meningitis and experimental autoimmune encephalomyelitis. 1063 96

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system (CNS) that is a model for multiple sclerosis. Previously, we showed that depletion of gamma delta T cells significantly reduced clinical and pathological signs of disease, which was associated with reduced expression of IL-1 beta, IL-6, TNF-alpha, and lymphotoxin at disease onset and a more persistent reduction in IFN-gamma. In this study, we analyzed the effect of gamma delta T cell depletion on chemokine and chemokine receptor expression. In the CNS of control EAE mice, mRNAs for RANTES, eotaxin, macrophage-inflammatory protein (MIP)-1 alpha, MIP-1 beta, MIP-2, inducible protein-10, and monocyte chemoattractant protein-1 were detected at disease onset, increased as disease progressed, and fell as clinical signs improved. In gamma delta T cell-depleted animals, all of the chemokine mRNAs were reduced at disease onset; but at the height of disease, expression was variable and showed no differences from control animals. mRNA levels then fell in parallel with control EAE mice. ELISA data confirmed reduced expression of MIP-1 alpha and monocyte chemoattractant protein-1 at disease onset in gamma delta T cell-depleted mice, and total T cell numbers were also reduced. In normal CNS mRNAs for CCR1, CCR3, and CCR5 were observed, and these were elevated in EAE animals. mRNAs for CCR2 were also detected in the CNS of affected mice. Depletion of gamma delta T cells reduced expression of CCR1 and CCR5 at disease onset only. We conclude that gamma delta T cells contribute to the development of EAE by promoting an inflammatory environment that serves to accelerate the inflammatory process in the CNS.
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PMID:Experimental autoimmune encephalomyelitis on the SJL mouse: effect of gamma delta T cell depletion on chemokine and chemokine receptor expression in the central nervous system. 1065 66

DA, GDVII and H101 are neurovirulent strains of Theiler's murine encephalomyelitis virus that cause very different neuropathology and CNS disease when inoculated into SJL/J mice. DA virus causes a chronic demyelinating disease, GDVII virus causes an acute fatal polioencephalomyelitis, and H101 virus causes an acute pachymeningitis with hydrocephalus. Performing RNase protection assays, we detected the same pattern of chemokine (RANTES, MCP-1, IP-10, MIP-1beta, MIP-1alpha and MIP-2) mRNA expression in brain and spinal cord during all three infections. In contrast, IFN-beta and IL-6 mRNA were highly expressed only in GDVII virus infection, whereas high levels of LT-alpha mRNA were only found during DA virus infection. Our study demonstrates that proinflammatory cytokines are involved in the neuropathogenesis of CNS disease and modulate the acute and chronic process underlying different pathologic features of disease.
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PMID:Alterations in cytokine but not chemokine mRNA expression during three distinct Theiler's virus infections. 1068 11

To investigate the mechanism for the resistance of IL-6-deficient mice to experimental autoimmune encephalomyelitis (EAE), we examined the production of cytokines in lymph nodes (LNs) of wild-type and IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) by reverse transcriptase-polymerase chain reaction analysis. Significant up-regulation of IL-4 production and down-regulation of IFN-gamma production were found in LNs from IL-6-deficient mice as compared to LNs from wild-type mice. Administration of IL-6, which caused typical EAE in IL-6-deficient mice immunized with MOG, reduced IL-4 production but did not restore IFN-gamma production in LNs of IL-6-deficient mice. These results implied that the resistance of IL-6-deficient mice to EAE might be mainly due to enhancement of Th2 response.
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PMID:Enhancement of Th2 response in IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein. 1074 53

This study was undertaken to better understand the role of cytokines in the pathogenesis, especially in the mechanisms of relapse, of experimental autoimmune encephalomyelitis (EAE). For this purpose, we induced acute and chronic relapsing (CR) EAE in DA rats and determined several immunological parameters in rats at various stages of two types of EAE. Histopathological analysis revealed that there was no significant difference in the severity of inflammation in the spinal cord lesions between the two groups. However, demyelination was observed only in rats with CR EAE. Cytokine analysis by competitive PCR demonstrated that levels of TNF-alpha, IL-6 and IL-12 p40 mRNA in the spinal cord at the first attack of CR EAE were significantly higher than those at the peak stage of acute EAE. The mRNA expression of anti-inflammatory cytokines, IL-10 and TGF-beta1, was generally low in both acute EAE and the first attack of CR EAE and upregulated at later stages of CR EAE. These findings suggest that persistent high-level expression of pro-inflammatory cytokines is closely associated with demyelination and relapse of EAE. In contrast, anti-inflammatory cytokines play only a minor role in the relapse.
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PMID:Characterization of acute versus chronic relapsing autoimmune encephalomyelitis in DA rats. 1090 Mar 51

Cytokines orchestrate T cell-mediated immune responses. In experimental autoimmune encephalomyelitis (EAE) the proinflammatory cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-12 and IL-18 are critically involved in the initiation and amplification of the local immune response in the CNS which is counter-balanced by upregulation of antiinflammatory cytokines such as IL-10. The predicted function of individual cytokines during EAE has recently been challenged by transgenic animal studies and neutralization experiments. Cytokine induction is not restricted to autoimmunity in the nervous system. Cytokines are involved in nerve regeneration and induced in focal cerebral ischemia both at the site of infarction and in remote nonischemic brain regions. In cerebral ischemia TNF-alpha and IL-1beta probably have dual functions: In concert with upregulation of inducible NO synthase (iNOS) they exert neurotoxicity while in the absence of iNOS, TNF-alpha and IL-1beta may contribute to neuroprotection and plasticity. The interplay between glial cells, infiltrating leukocytes and induced cytokines leading to CNS pathology is complex and incompletely understood. Further assessment of the functional contribution of cytokines critically depends on the elucidation of downstream secondary signaling mechanisms.
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PMID:Cytokines in CNS disorders: neurotoxicity versus neuroprotection. 1096 21

This study addresses the issue of the effect of immunomodulating therapies in the target organ-the central nervous system (CNS)-in the case of multiple sclerosis. Copolymer 1 (Cop 1, Copaxone, glatiramer acetate), an approved drug for the treatment of multiple sclerosis, is a potent inducer of Th2 regulatory cells in both mice and humans. Highly reactive Cop 1-specific T cell lines that secrete IL-4, IL-5, IL-6, IL-10, and transforming growth factor-beta in response to Cop 1 and crossreact with myelin basic protein (MBP) at the level of Th2 cytokine secretion were established from both brains and spinal cords of Cop 1-treated mice. In contrast, no reactivity to the control antigen lysozyme could be obtained in lymphocytes isolated from CNS of mice injected with lysozyme. Adoptively transferred labeled Cop 1-specific suppressor cells were found in brain sections 7 and 10 days after their injection to the periphery, whereas lysozyme-specific cells were absent in the CNS. Hence, Cop 1-induced Th2 cells cross the blood-brain barrier and accumulate in the CNS, where they can be stimulated in situ by MBP and thereby exert therapeutic effects in the diseased organ. This therapeutic effect was manifested, in brains of experimental autoimmune encephalomyelitis-induced mice, by a decrease in the inflammatory cytokine interferon-gamma and by secretion of the anti-inflammatory cytokine IL-10 in response to the autoantigen MBP.
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PMID:Specific Th2 cells accumulate in the central nervous system of mice protected against experimental autoimmune encephalomyelitis by copolymer 1. 1102 47


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