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)

Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is a self-limited inflammatory process localized to the central nervous system that is induced by the injection of myelin basic protein (MBP) in adjuvant. Oral administration of MBP suppresses EAE, and this suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress both in vitro and in vivo by the release of transforming growth factor (TGF) beta after antigen-specific triggering. Furthermore, oral tolerance to MBP is enhanced by the concomitant oral administration of lipopolysaccharide (LPS). The present study was undertaken to determine whether the disease course in EAE and its suppression by oral tolerization to MBP is associated with distinct patterns of cytokine expression in the target organ. Detailed immunohistology of the brain was performed at the peak of clinical disease (day 14 after immunization) and after recovery (day 18) in control (ovalbumin [OVA]-fed), MBP-fed, and MBP plus LPS-fed animals. Brains from OVA-fed animals at the peak of disease showed perivascular infiltration with activated mononuclear cells which secreted the inflammatory cytokines interleukins (IL) 1, 2, 6, 8, TNF-alpha, and interferon gamma. The inhibitory cytokines TGF-beta and IL-4, and prostaglandin E2 (PGE2) were absent. In MBP orally tolerized animals there was a marked reduction of the perivascular infiltrate and downregulation of all inflammatory cytokines. In addition, there was upregulation of the inhibitory cytokine TGF-beta. In MBP plus LPS orally tolerized animals, in addition to upregulation of TGF-beta and reduction of inflammatory cytokines, there was enhanced expression of IL-4 and PGE2, presumably secondary to activation of an additional population of immunoregulatory cells. In OVA-fed animals that had recovered (day 18), staining for inflammatory cytokines diminished, and there was the appearance of TGF-beta and IL-4. These results suggest that suppression of EAE, either induced by oral tolerization or that which occurs during natural recovery is related to the secretion of inhibitory cytokines or factors that actively suppress the inflammatory process in the target organ.
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PMID:Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain. 138 85

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system. The effect of the immunosuppressive molecule transforming growth factor-beta, (TGF-beta 1) on chronic relapsing EAE produced by the transfer of myelin basic protein-specific T cell lines was studied. TGF-beta 1 markedly inhibited the activation and proliferation of myelin-basic protein-specific lymph node cells in vitro. This reduced the capacity of these cells to transfer EAE. In addition, administration of TGF-beta 1 in vivo consistently resulted in an improved clinical course, even when given during ongoing disease. Immunopathologic study demonstrated a marked reduction in central nervous system damage and expression of cell-surface lymphocyte function-associated Ag-1 and class II MHC molecules in TGF-beta 1-treated mice. These findings have identified TGF-beta 1 as a possible therapeutic agent for the human demyelinating disease multiple sclerosis.
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PMID:Prevention and treatment of chronic relapsing experimental allergic encephalomyelitis by transforming growth factor-beta 1. 170 29

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine with immunosuppressive effects on T cells in vitro. Experimental allergic encephalomyelitis is an archetypal T cell-mediated autoimmune demyelinating disease of the central nervous system that often serves as a model for multiple sclerosis. In vivo administration of TGF-beta 1 into SJL mice was successful in reducing the incidence of clinical disease and the histologic severity of inflammation and demyelination in the brain and spinal cord. Immunohistochemical studies performed on control animals showed that TGF-beta-1, -2, and -3 were present in inflammatory perivascular lesions in the brain. The use of a naturally occurring cytokine with immunoregulatory functions in the treatment of an autoimmune disease is novel. However, potential long term complications of such therapy must be addressed before its use in human autoimmune disease such as multiple sclerosis.
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PMID:Successful treatment of experimental allergic encephalomyelitis with transforming growth factor-beta 1. 171 79

Borna disease is a virus-induced, immune-mediated encephalomyelitis based on a delayed-type hypersensitivity reaction. The severity of clinical symptoms after intracerebral infection of rats with Borna disease virus was reduced after treatment with transforming growth factor (TGF-beta 2). Intraperitoneal injection of the recombinant molecule, rTGF-beta 2, started on the day of infection at a dose of either 1 micrograms given every day or every other day for 8 consecutive days or 2 micrograms every third day, was found to result in the absence of typical Borna disease symptoms at 14 days after infection in most of the TGF-beta-treated rats, a time point at which all infected control animals not treated with rTGF-beta 2 showed distinct signs of Borna disease. The inhibition of the disease was paralleled by a significant reduction of the inflammatory reaction in the brain. However, the efficacy of treatment with rTGF-beta 2 was transient, because after day 21 only a slight or no reduction of the inflammatory reaction and, consequently, symptoms of Borna disease could be observed. Immunohistologic investigations revealed reduced CD4+ T cell numbers and no changes in macrophage counts in encephalitic lesions of rTG-beta treated rats. However, CD8+ cells were markedly decreased in the encephalitic lesions. Furthermore, the expression of MHC class II Ag was significantly reduced in the brain of rTGF-beta 2 treated Borna disease virus-infected rats, whereas MHC class I Ag expression was not. Most treated animals showed a reduction of Borna disease virus-specific serum antibodies, the result of an inhibition of the IgG response. The results presented here suggest a distinct influence of rTGF-beta 2 on T cell-mediated immune functions during the early phase of Borna disease virus-induced encephalomyelitis.
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PMID:Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8+ cells and suppression of antibody formation. 194 Mar 57

Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively. When administered during induction of the disease, TGF-beta 1 prevents CIA but only delays the onset of REAE by 2-3 days. However, when administered during a remission. TGF-beta 1 prevents the occurrence of relapses in REAE. The results suggest that TGF-beta 1 has powerful anti-inflammatory effects, mimicking in some respects the beneficial effects of immunosuppressive drugs in these experimental models of autoimmune disease, but without discernable adverse effects.
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PMID:Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice. 201

The transforming growth factors (TGF) type beta 1 and beta 2 are regulatory cytokines strongly affecting rat astrocyte immune functions. Both cytokines suppressed presentation of autoantigen by astrocytes: highly encephalitogenic T cells cocultured with TGF-beta-treated astrocytes in the presence of myelin basic protein did not become activated to transfer experimental allergic encephalomyelitis, a central nervous system (CNS) autoimmune disease. Furthermore, TGF-beta 1 and -beta 2 antagonized hyperinduction of astrocyte major histocompatibility complex (MHC) class II antigen expression by interferon-gamma and tumor necrosis factor-alpha. Thus, TGF-beta might be a potential regulator of CNS inflammation.
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PMID:Transforming growth factors type beta 1 and beta 2 suppress rat astrocyte autoantigen presentation and antagonize hyperinduction of class II major histocompatibility complex antigen expression by interferon-gamma and tumor necrosis factor-alpha. 210 88

The transforming growth factors TGF-beta 1 and beta 2 are cytokines with pronounced effects on leukocyte growth and function. To evaluate a potential use of these factors as immunosuppressive agents, we compared the effects of TGF-beta 1 and beta 2 on autoimmune T cells in rat inflammatory central nervous system disease, experimental allergic encephalomyelitis (EAE). We observed that both factors strongly inhibited in vitro activation of autoimmune T cells, suppressed the accumulation of interleukin-2 mRNA and decreased the expression of rat T cell activation antigens. In addition, cyclical changes in susceptibility to TGF-beta was observed with T line cells. The modulation of in vitro T cell function is associated with a considerable suppression of encephalitogenic capacity of autoimmune T line cells. Thus, TGF-beta 1 and beta 2 might have physiologic importance in limiting local T lymphocyte proliferation and effector function in autoimmune disease.
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PMID:Transforming growth factors beta 1 and beta 2: cytokines with identical immunosuppressive effects and a potential role in the regulation of autoimmune T cell function. 280 92

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.v. induces mild relapses in 50% of such mice. In addition, tumor necrosis factor (TNF)-alpha (0.2 micrograms, i.p.) also induces EAE relapses in 43% of SJL mice when injected 1-2 months after recovery. SEB does not induce a second relapse if reinjected when V beta 17a+T cells are still partially deleted. In these mice, however, TNF-alpha is equally effective in inducing relapses as in mice that did not receive SEB previously. We showed earlier that transforming growth factor (TGF)-beta and TNF-alpha have antagonistic effects on experimental autoimmune diseases; e.g., in spontaneously relapsing EAE, TGF-beta and anti-TNF were protective, while anti-TGF-beta caused disease exacerbation. Interleukin (IL)-10 is also known to counteract certain TNF effects. We now find that both human IL-10 and TGF-beta 2 lower the incidence of EAE relapses when given simultaneously with SEB or TNF-alpha. The protective effect of TGF-beta is significant only against relapses induced by SEB (reduced to 9%), and that of IL-10 only against relapses induced by TNF (reduced to 0%) with the treatment regimens employed. Neutralizing anti-TGF-beta does not increase the incidence of SEB-induced EAE relapses. In contrast, anti-IL-10 increases both the incidence and the severity of such relapses. We conclude that TNF production is probably important in causing EAE relapses, but that other aspects of the SEB-induced reactivation of myelin-specific T cells also contribute. Furthermore, endogenous IL-10 rather than TGF-beta production appears to limit the susceptibility to induction of EAE relapses in this model.
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PMID:Staphylococcal enterotoxin B and tumor-necrosis factor-alpha-induced relapses of experimental allergic encephalomyelitis: protection by transforming growth factor-beta and interleukin-10. 748 40

Polymorphism of the major histocompatibility complex (MHC) influences susceptibility to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP) in rats. Current concepts relate such influences to the capacity of class II molecules to present relevant peptides to autoreactive T cells. We have here analyzed the MHC influence on the immune response and the development of EAE after immunization with the immunodominant peptide MBP-63-88. Analysis of MHC-congenic LEWIS strains showed that RT1a, RT1c and RT1(1) haplotypes are permissive for disease induction, whereas RT1d and RT1u are resistant. All EAE responding strains showed peptide-specific proliferation and interferon (IFN)-gamma secretion, but no early significant tendency to express interleukin (IL-4) or transforming growth factor (TGF)-beta mRNA in lymphocytes in response to the MBP 63-88, 7 days post immunization (p.i.). Later, 14 days p.i., peptide-specific induction of IL-4 and TGF-beta occurred in RT1(1) rats. Among the EAE non-responders strains, only the RT1u rats showed an immune response to MBP 63-88. This response, however, was qualitatively different from the immune response in the EAE-susceptible strains. Thus, there was no proliferation and only moderate IFN-gamma production in response to peptide, but in contrast, a significant and early peptide-induced IL-4 and TGF-beta response was observed. The data suggest that the MHC-associated susceptibility to EAE is partly related to the ability to mount a TH1-like immune response while the MHC-associated EAE resistance may either be related to MBP peptide non-responsiveness or to peptide recognition and induction of a qualitatively different and disease down-regulatory immune response.
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PMID:The major histocompatibility complex influences myelin basic protein 63-88-induced T cell cytokine profile and experimental autoimmune encephalomyelitis. 750 88

We have been studying the suppression of experimental autoimmune encephalomyelitis in the Lewis rat after oral administration of myelin basic protein (MBP). Suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress immune responses in vitro. This suppression is mediated by secretion of TGF-beta following triggering by the fed antigen. In the present study, we tested the ability of overlapping 20 amino acid peptides from MBP to trigger suppression mediated by spleen cells from Lewis rats orally tolerized to MBP. Using a transwell system, we found that spleen cells from MBP orally tolerized animals stimulated by residues 21-40, 51-70 and 101-120 of MBP suppress proliferative responses of an ovalbumin specific cell line. This suppression correlated with secretion of TGF-beta by cells stimulated with the peptide. In addition, T cells from animals fed the tolerogenic peptide 21-40 alone secreted TGF-beta whereas no TGF-beta release or in vitro suppression was observed in animals fed the MBP encephalitogenic determinant 71-90. The 71-90 peptide triggered proliferation of MBP primed cells from animals immunized with MBP/CFA whereas the suppressor epitopes identified above did not. Furthermore, oral administration of peptide 21-40 suppressed disease induced by peptide 71-90. DTH responses to 71-90 were not affected by oral administration of peptide 21-40 whereas DTH responses to whole MBP were suppressed. These results demonstrate that distinct suppressor determinants exist on MBP which are separate from encephalitogenic determinants, and that epitope-driven bystander suppression plays an important role in down-regulation of tissue specific autoimmune processes following oral tolerization. These findings have important implications for the design of tissue specific targeted immunotherapy by oral tolerization in humans.
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PMID:Epitopes of myelin basic protein that trigger TGF-beta release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression. 750 26


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