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)

A protracted and relapsing form of experimental allergic encephalomyelitis (EAE) develops in the DA rat after immunization with rat spinal cord homogenate (SCH) emulsified in incomplete Freund's adjuvant (IFA). The genetic influence on this model has been analyzed by immunizing MHC congenic strains on both LEW and DA genetic backgrounds, and recombinant inbred strains between DA and E3 rats. An in situ hybridization assay was used to examine the expression of mRNA for IFN-gamma, IL-4, IL-10 and transforming growth factor (TGF)-beta both in sections of spinal cords and the antigen-induced expression for these cytokines by splenocytes after in vitro stimulation with encephalitogenic MBP peptides. The susceptibility of relapsing EAE after immunization with SCH in IFA in the DA strain, but not the E3 strain, was correlated with a lack of expression for TGF-beta in the spinal cord. The recombinant inbred DXEB rats developed a severe EAE while surprisingly no signs of disease were observed in the DXEA strain, which shares the MHC region with the DXEB strain, after immunization with the MBP 63-87 peptide. Resistance to relapsing EAE in the DXEA strain correlated with increased non-MHC controlled expression for TGF-beta and lack of IFN-gamma in the spinal cord. The same pattern of cytokine expression was seen in splenocytes after stimulation in vitro with the MBP 63-87 peptide. A spreading of the immune response to the MBP 87-110 peptide was seen. Non-MHC genes controlled the quality of this response: splenocytes from MBP 63-87 immunized DXEB rats responded in vitro towards the MBP 87-110 peptide by expressing mRNA for IFN-gamma, IL-10 and IL-4, whereas in the DXEA strain the corresponding response involved IL-4 and TGF-beta. Taken together these data show that non-MHC controlled expression of mRNA for TGF-beta is associated with resistance to EAE.
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PMID:Genetic influence on disease course and cytokine response in relapsing experimental allergic encephalomyelitis. 957 21

Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-mediated autoimmune disease directed against central nervous system (CNS) myelin antigens such as myelin basic protein (MBP). EaE is usually characterized by spontaneous remission of clinical disease and immune pathology despite the persistence of self myelin antigens in the central nervous system. Following induction of an acute episode of EAE, spontaneous remission also occurs in MBP T cell receptor (TCR) transgenic mice even through most T cells express a TCT specific for MBP. To investigate the mechanisms of recovery associated with EAE, we examined the behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during disease progression and recovery. We found that recovery from EAE was associated with three major immunologic changes: (1) deletion of encephalitogenic T cells in the brain; (2) deviation of MBP-specific transgenic (Tg+) T cells both in the periphery and in the central nervous system from INF- gamma secretin Th1 type cells to cells that secrete IL-4, IL-10, and TGF- beta ; and (3) deletion of Tg+ T cells in the thymus through apoptosis. Thus spontaneous recovery from a classic Th1 type organ specific autoimmune disease is associated with two mechanisms of immune tolerance, deletion of autoreactive cells and immune deviation of autoreactive cells to a non-pathogenic phenotype.
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PMID:Mechanisms of recovery from experimental autoimmune encephalomyelitis: T cell deletion and immune deviation in myelin basic protein T cell receptor transgenic mice. 958 11

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease of the central nervous system (CNS) that has served as the principal experimental model for multiple sclerosis (MS). Susceptibility to disease is thought to correlate with the ability to generate a Th1-type cytokine profile in myelin-responsive T cells, whereas T cells producing a Th2 cytokine pattern, in particular IL-4, are thought to be nonencephalitogenic and also to confer protection against a Th1-type response. However, recent studies using a variety of genetically engineered animals in which the genes for Th1-type cytokines and/or their receptors have been inactivated have called into question the Th1-Th2 paradigm in experimental allergic encephalomyelitis. In this report we have addressed the contribution of IL-4 to disease expression by studying two strains of mice, C57BL/6 and BALB/c, in which the gene for IL-4 has been inactivated. The IL-4-deficient C57BL/6 mice, and to a lesser extent the IL-4-deficient BALB/c mice, developed a more severe form of clinical disease, a more extensive pathologic involvement of the spinal cord, and an increased expression of proinflammatory cytokines in the CNS than their wild-type littermates. BALB/c and C57BL/6 mice showed a slightly different cytokine profile in the CNS. Both groups of animals recovered from the acute clinical episode in a time frame that was essentially identical to that found in the wild-type controls. We conclude that IL-4 plays an important role in modulating the severity of the encephalitogenic process, but does not by itself contribute to spontaneous remission from the disease.
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PMID:A critical role for IL-4 in regulating disease severity in experimental allergic encephalomyelitis as demonstrated in IL-4-deficient C57BL/6 mice and BALB/c mice. 959 Feb 29

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system with many similarities to multiple sclerosis. The main effector cells involved are CD4+ T cells, recognizing encephalitogenic epitopes within the central nervous system, and macrophages, both of which secrete proinflammatory cytokines, such as IFN-gamma and TNF. Studies have shown that immunomodulation of this inflammatory response by anti-inflammatory cytokines (IL-4, IL-10, IFN-beta, and TGF-beta) can reduce clinical severity in EAE. The importance of TNF in EAE has been demonstrated by using soluble TNF-receptor molecules to inhibit EAE. However, the limitation of this type of therapy is the necessity for frequent administration of cytokine proteins due to their short biologic half-life. This study demonstrates that EAE can be inhibited by a single injection of therapeutic cytokine (IL-4, IFN-beta, and TGF-beta) DNA-cationic liposome complex directly into the central nervous system. DNA coding for a novel, dimeric form of human p75 TNF receptor also ameliorated clinical EAE. Local administration of DNA-cationic liposome complex has identified gene targets that may be more efficiently exploited using vectors producing more stable expression for effective treatment of neuroimmunologic disease.
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PMID:Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system. 959 Feb 71

Recombinant interferon beta (IFNbeta) benefits patients with relapsing remitting multiple sclerosis (MS), but the mechanisms of action are unknown. We studied in vivo immunologic effects of IFNbeta treatment and their relationship to clinical efficacy. Cytokines were measured in blood and CSF from MS patients participating in a placebo-controlled phase III clinical trial and an open-label phase IV [corrected] tolerability study of IFNbeta-1a. Additionally, immunologic studies were conducted in animals with proteolipid protein (PLP)-induced chronic relapsing experimental autoimmune encephalomyelitis. Single intramuscular (IM) injections of IFNbeta-1a (6 MIU, 30 microg) were associated with significant in vivo upregulation of interleukin-10 (IL-10) and IL-4 but not IFNgamma mRNA in peripheral blood mononuclear cells. Forty-eight hours after each IFNbeta-1a injection, serum IL-10 levels increased and remained elevated for 1 week. IFNbeta-1a recipients in the placebo-controlled phase III clinical trial showed significantly increased concentrations of CSF IL-10 after 2 years of treatment. This response correlated with a favorable therapeutic response. Exposure of PLP-reactive murine T-cell lines to IFNbeta resulted in increased antigen-driven expression of IL-4 and IL-10 and reduced encephalitogenicity. IFNbeta-1a injections induce systemic and intrathecal immunosuppressive cytokines. Myelin-specific T cells treated with IFNbeta-1a demonstrate increased immunosuppressive cytokine expression and reduced encephalitogenicity. The relationship between increased CSF IL-10 and response to therapy suggests that induction of IL-10 is a mechanism underlying IFNbeta-1a effects in MS patients.
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PMID:In vivo effects of interferon beta-1a on immunosuppressive cytokines in multiple sclerosis. 959 77

Previously we demonstrated that 1,25-dihydroxyvitamin D3 blocks the progression of relapsing encephalomyelitis. We now propose that 1,25-dihydroxyvitamin D3 blocks these autoimmune symptoms by stimulating the differentiation and/or function of cells that inhibit the encephalitogenic process. To support this belief, we have found that 1,25-dihydroxyvitamin D3 administration to mice increases IL-4 transcripts by 3- to 25-fold and TGF-beta 1 transcripts by 4- to 24-fold. Similarly, IL-4 and TGF-beta 1 transcripts were higher in the central nervous system of 1,25-dihydroxyvitamin D3-treated mice compared with controls. The number of cells recoverable from the lymph nodes of 1,25-dihydroxyvitamin D3-treated mice was only 50% that of controls. Overall, 1,25-dihydroxyvitamin D3 treatment causes a net loss in the total number of lymphocytes while the number of IL-4 and TGF-beta 1 transcripts increased. The systemic and local increase in the expression of these two anti-inflammatory cytokines by 1,25-dihydroxyvitamin D3 may be responsible for the ability of this drug to block encephalomyelitis.
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PMID:1,25-dihydroxyvitamin D3 is a positive regulator for the two anti-encephalitogenic cytokines TGF-beta 1 and IL-4. 960 30

CD4+ T cells may be assigned a functional status (Th1 or Th2) according to the cytokines they produce including IL-2, IFN-gamma and IL-4. Th1 and Th2 CD4+ T cells deliver different isotype-switching signals to antigen-specific B cells which bias the serum Ig isotypes. The stimulation of Th1 or Th2 responses is influenced by adjuvants and administration of antigen in IFA results in Th1 unresponsiveness as evidenced by: (i) reduced T cell proliferation to antigen; (ii) reduced IFN-gamma production in response to antigen; and (iii) reduced IgG2a isotype antigen-specific antibodies following antigen/CFA challenge. The impact of established human gamma globulin (HGG) specific Th1 unresponsiveness on subsequent immunization with an unrelated antigen, human serum albumin (HSA) in Th1-inducing CFA was then examined. When subsequently challenged with a mixture of HSA and HGG in CFA the HGG-specific Th1 unresponsiveness was infectious and dominant, preventing the induction of a Th1 response to HSA. Reduced T cell proliferation, IFN-gamma production and IgG2a antibody were consequently observed in response to HSA. The HGG-specific Th1 unresponsiveness was not infectious when HGG/CFA and HSA/CFA were administered at separate sites. This demonstrates that antigen-specific Th1 unresponsiveness can be infectious for new, molecularly unrelated antigens and supports studies showing that Th1-mediated autoimmune diseases such as experimental allergic encephalomyelitis (EAE) and diabetes can be ameliorated using antigens molecularly distinct from the disease-inducing immunogen.
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PMID:Th1 unresponsiveness can be infectious for unrelated antigens. 961 88

Theiler's murine encephalomyelitis virus (TMEV) induced demyelinating disease, is an animal model of multiple sclerosis (MS). The viral-induced encephalitis is followed by an inflammatory and demyelinating disease. We quantitated the response of female and male mice during the transition from encephalitis to early demyelination. CNS neuropathology and antiviral antibody production were evaluated. Parallel studies were done with anti-inflammatory cytokines IL-4, IL-10 or a combination of IL-4 with IL-10. Results show female mice demonstrate an augmented susceptibility to the virus and a greater response to the cytokine therapies. Significant variation was noted during early demyelinating disease. The combination therapy of IL-4 with IL-10 produced striking decreases in antiviral antibody levels and virus-induced neuropathologic disease. Male mice are less susceptible to viral-induced disease and are less responsive to the cytokine treatments. Gender bias in TMEV-induced demyelinating disease appears to parallel the differences noted with other experimental immune diseases.
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PMID:Gender variations in early Theiler's virus induced demyelinating disease: differential susceptibility and effects of IL-4, IL-10 and combined IL-4 with IL-10. 962 96

Linomide (quinoline-3-carboxamide) is a synthetic immunomodulator that suppresses several experimental autoimmune diseases. Here we report the effects of Linomide on experimental autoimmune encephalomyelitis (EAE), a CD4+ T cell-mediated animal model of multiple sclerosis (MS). EAE induced in Lewis rats by inoculation with homogenized guinea pig spinal cord and Freund's complete adjuvant was strongly suppressed by Linomide administered daily subcutaneously from the day of inoculation. Linomide dose-dependently delayed the interval between immunization and onset of clinical EAE, and reduced severity of EAE symptoms. These clinical effects were associated with dose-dependent down-modulation of myelin antigens-induced T cell responses and by suppression of the proinflammatory cytokines IFN-gamma and TNF-alpha, and upregulation IL-4, IL-10 and TGF-beta as evaluated by in situ hybridization for mRNA expression in spleen mononuclear cells and spinal cord sections. These findings suggest that Linomide could be useful in certain T cell dependent autoimmune diseases.
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PMID:Linomide suppresses acute experimental autoimmune encephalomyelitis in Lewis rats by counter-acting the imbalance of pro-inflammatory versus anti-inflammatory cytokines. 963 Jan 63

Interleukin 10 (IL-10) is an important anti-inflammatory cytokine. To examine its role in virus-induced encephalomyelitis, IL-10-deficient (IL-10 -/-) mice were infected with a neurotropic strain of mouse hepatitis virus (JHMV). JHMV-infected IL-10 -/- mice, compared to IL-4 -/- and syngeneic C57BL/6 mice, exhibited increased morbidity and mortality. Virus was cleared from the CNS of all groups of mice with equal kinetics by day 9 postinfection and the lack of either IL-4 or IL-10 did not alter the distribution of viral antigen, suggesting a lack of correlation between viral replication and the increased clinical disease in IL-10 -/- mice. In moribund IL-10 -/- mice, a moderate increase in mononuclear cell infiltration was correlated with increased expression of tumor necrosis factor-alpha, interferon-gamma, and inducible nitric oxide synthase mRNAs. In the small percentage of IL-10 -/- mice that survived, no differences in either demyelination or inflammation were observed. Together, these results suggest that IL-10 is not required for viral clearance, and although it appears to be one of the mechanisms responsible for inhibiting the extent of inflammation in the CNS during acute JHMV infection, it has little role in the eventual resolution of CNS inflammatory responses.
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PMID:The role of IL-10 in mouse hepatitis virus-induced demyelinating encephalomyelitis. 963 66


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