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)

Immunization of Lewis rats with guinea-pig myelin basic protein (Gp-MBP) induced T cell responses to primary and secondary encephalitogenic determinants, as well as to a third non-encephalitogenic epitope, residues 55-69. This sequence is of interest due to its protective activity against experimental autoimmune encephalomyelitis. Protection involved induction of MBP-55-69-specific T cells expressing cross-reactive TCR BV8S6 genes that activated regulatory T cells specific for TCR BV8S2 determinants expressed on encephalitogenic T cells. We here present and discuss new evidence suggesting a possible immunological cross-reactivity between the protective Gp-MBP-55-69 peptide and the regulatory BV8S2-39-59 peptide. This cross-reactivity, which may also occur between the human MBP-55-74 peptide and the BV12S2-38-58 sequence, has potentially important implications for human diseases such as multiple sclerosis.
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PMID:Effects of vaccination with T cell receptor peptides: epitope switching to a possible disease-protective determinant of myelin basic protein that is cross-reactive with a TCR BV peptide. 955 80

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

IFN-beta has recently been shown to exert remarkable beneficial effects on disease development in patients with early stage relapsing-remitting MS. The specific immune mechanism(s) by which IFN-beta ameliorates this human demyelinating disease is at present undefined. One potential mechanism may reside in the antiproliferative activity of IFN-beta which may inhibit the expansion of autoaggressive T cells thereby limiting disease progression. In the present study we investigated whether the administration of recombinant rat IFN-beta (rrIFN-beta) to Lewis rats with actively induced experimental autoimmune encephalomyelitis (EAE) inhibits the expansion of encephalitogenic T cells in lymphoid organs and as such may contribute to suppression of disease activity in this widely used animal model for MS. Our data show that daily administrations of > or = 3 x 10(5) u rrIFN-beta to EAE rats, starting two days before MBP sensitization and continued for 10 days led to a dramatic and dose-dependent reduction in encephalitogenic T cells in both spleen and inguinal lymph nodes at day 8 post-immunization (p.i.). However, the rrIFN-beta-mediated reduction in effector T cells did not ameliorate paralytic disease as expected but significantly enhanced the severity of EAE. Analyses of lymphoid organs in the remission phase of EAE revealed strongly elevated numbers of encephalitogenic T cells in rrIFN-beta-treated versus control rats suggesting a rapid reversal of the antiproliferative action of rrIFN-beta followed by an overshoot in the subsequent expansion of these effector T cells. In conformity with higher numbers of encephalitogenic T cells and worsening of disease, animals also showed significantly greater perivascular inflammation in the CNS. The relevance of our findings in relation to the beneficial effects of IFN-beta in MS is discussed.
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PMID:Discontinuation of treatment with IFN-beta leads to exacerbation of experimental autoimmune encephalomyelitis in Lewis rats. Rapid reversal of the antiproliferative activity of IFN-beta and excessive expansion of autoreactive T cells as disease promoting mechanisms. 960 Jul 4

Considering the role of pleiotropic interleukin-1 (IL-1) in inflammation and autoimmunity, studies were designed to examine whether specific blockade of IL-1 may influence these processes in the CNS. Although the role of CD4+ T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis (EAE) has been unequivocally demonstrated, the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined. We have evaluated the effect of human recombinant interleukin-1 receptor antagonist (IL-1Ra) in vivo on the course of actively induced EAE in highly susceptible Dark Agouti (DA) rats. The rats which were treated during the induction phase of disease (days 0-6) with IL-1Ra (350 microg/rat/day) developed milder signs of EAE, when compared to saline-treated control animals immunized with encephalitogen, which developed severe single episode disease. The transfer of lymph node cells (LNC) isolated from MBP-primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients. However, rats injected with LNC that have been stimulated in vitro in the presence of IL-1Ra (10 microg/ml) developed significantly milder disease. Diminished encephalitogenic capacity of LNC correlated with lower proliferative response to antigen and mitogen and decreased expression of IL-2 receptors. These data provide further evidence that IL-1 is an important factor for activation of EAE inducing T lymphocytes.
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PMID:Interleukin-1 receptor antagonist suppresses experimental autoimmune encephalomyelitis (EAE) in rats by influencing the activation and proliferation of encephalitogenic cells. 962 1

We have previously shown that interferon-tau (IFN-tau) pretreatment inhibits the development of both acute and chronic mouse experimental allergic encephalomyelitis (EAE), an animal model for the human demyelinating disease multiple sclerosis (MS). IFN-tau is a type I IFN that has pregnancy recognition hormone activity in ruminants. Here we show that IFN-tau induced remission in SJL/J mice that had ongoing chronic active EAE disease and protected mice against secondary relapses. IFN-tau treatment reversed lymphocyte infiltration and microglial activation in the central nervous system. Mice that were treated with IFN-tau had lower levels of anti-MBP antibodies than untreated mice in both chronic and acute forms of EAE. MBP induced proliferation in B cells from EAE mice, but treatment with IFN-tau either in vivo or in vitro blocked activation. Furthermore, IFN-tau inhibited MBP activation of T cells from EAE mice. Thus, IFN-tau inhibits the humoral arm as well as the cellular arm of the autoimmune disease EAE. The data presented here show that IFN-tau inhibits both B cell and T cell responses in EAE as well as active, chronic EAE, and this may help explain the effectiveness of type I IFNs in treatment of MS.
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PMID:IFN-tau suppresses both the autoreactive humoral and cellular immune responses and induces stable remission in mice with chronic experimental allergic encephalomyelitis. 966 51

L-selectin is an adhesion molecule expressed on T cells and monocytes. It mediates rolling--the initial step of transendothelial migration. In this study, we investigated the role of L-selectin in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in Lewis rats by active sensitization with myelin basic protein (MBP-EAE), or by adoptive transfer using MBP specific T cells (AT-EAE). Treatment with HRL3, a monoclonal antibody to L-selectin, and its F(ab')2 fragments efficiently suppressed MBP-EAE, and had a mild inhibitory effect on AT-EAE. Histological examination revealed a marked reduction of inflammatory infiltrates after treatment with HRL3. Administration of the control antibody HRL4 did not significantly alter the course of the disease. HRL3 caused T-cell depletion in the draining lymph nodes and spleen and a downregulation of L-selectin expression on T cells. We conclude that L-selectin-dependent mechanisms are involved in the pathogenesis of EAE. Modulation of L-selectin in vivo by antibodies or by competitive antagonists could be a novel therapeutic approach to autoimmune diseases of the central nervous system.
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PMID:Role of the leukocyte-adhesion molecule L-selectin in experimental autoimmune encephalomyelitis. 974 95

Emerging data suggest that polymorphonuclear leukocytes (PMNLs) can play an important role in Ag-dependent immune responses. Therefore, we have assessed the involvement of these cells in the development of an organ-specific autoimmune disease, experimental autoimmune encephalomyelitis (EAE), in the mouse. Depletion of peripheral blood PMNLs beginning day 8 after immunization significantly delayed and in some cases totally prevented the development of clinical EAE in mice. Depletion of PMNLs beginning 1 day before sensitization and continuing until day 7 postimmunization had no effect on the subsequent development of EAE, suggesting that depletion alters the efferent but not the afferent arm of the immune response. In vitro studies showed that lymphoid cells from mice protected from EAE by PMNL depletion beginning on day 8 postsensitization proliferated in response to specific Ag to a level equal to cells from sensitized animals treated with control serum, again indicating that treatment was not affecting the afferent limb of the immune response. Further evidence that PMNL may be necessary in initiating the pathology of EAE was seen in passive transfer experiments where PMNL-depleted recipients of MBP-specific lymphoid effector cells developed EAE much less effectively than did animals treated with control Ab. Taken together, these data indicate that PMNLs play a critical role in the effector phase of the development of the clinicopathologic expression of EAE in mice.
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PMID:Treatment with anti-granulocyte antibodies inhibits the effector phase of experimental autoimmune encephalomyelitis. 983 34

An in vivo magnetic resonance (MR) imaging study was performed on experimental allergic encephalomyelitis (EAE) induced in Lewis rats through proteolipid protein (PLP). PLP was solubilized in water or in an aqueous solution of 1% 10-tridecyl ether (TDE), a non-ionic detergent used in membrane protein research. All 16 rats immunized with 500 microg of TDE-solubilized PLP developed clinical signs and MR abnormalities fully comparable to those observed in MBP-induced EAE. Total paraplegia was observed in 12.5% of rats, mild or moderate paraparesis in 68.8% of rats and tail paralysis in the remaining 18.7% of rats. Whereas only 37.5% of the eight rats immunized with 500 microg of water-solubilized PLP developed minor clinical signs (tail weakness or paralysis). Our observations confirm that the difficulties encountered when trying to induce EAE by means of PLP arise from the highly hydrophobic nature of this protein. Accordingly, if a reproducible model is to be developed, it seems more judicious to use non-ionic detergents in both the extraction and solubilization phases of PLP preparation, this would allow maximal solubilization of the protein while avoiding aggregates, which may otherwise form during either of the PLP preparation.
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PMID:Magnetic resonance imaging of PLP-induced experimental allergic encephalomyelitis in Lewis rats. 991 76

A phosphodiesterase inhibitor (PDEI), Ibudilast, which has been in wide use for the management of bronchial asthma and cerebrovascular disease in Japan, was tested for its clinical efficacy on experimental autoimmune encephalomyelitis (EAE) in Dark August rats. The severity of acute EAE was significantly ameliorated by prophylactic oral treatment with Ibudilast (10 mg/kg per day) starting on the day of immunization, although it did not modify the course of the disease when it was given after the onset of the first clinical sign of EAE. Histologically, inflammatory cell infiltration in the lumbar spinal cord was significantly reduced in Ibudilast-treated animals as compared to control animals. Ibudilast mildly suppressed MBP-induced proliferation of T cells in regional lymph nodes, the secretion of interferon-gamma from T cells activated by MBP in CFA, and the secretion of tumor necrosis factor-alpha from macrophages. While the in vitro studies did not suggest difference between Ibudilast and other PDEIs such as rolipram, the clinical dose of Ibudilast is approximately 200-fold higher than that of rolipram and the effective dose of Ibudilast was relatively close to what has been therapeutically used in patients. Thus, Ibudilast may be a candidate for clinical use for patients with multiple sclerosis. 1999 Elsevier Science B.V. All rights reserved.
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PMID:Ibudilast, a phosphodiesterase inhibitor, ameliorates experimental autoimmune encephalomyelitis in Dark August rats. 1022 13

Transgenic Lewis rats overexpressing proteolipid protein (PLP) genes in peripheral and central nervous myelin were produced by microinjecting murine genomic PLP sequences into fertilized eggs. The mouse PLP gene shares 98.7% homology in the nucleotide sequence with its rat counterpart, but both are fully identical on protein level. Homozygous rats show tremors early in postnatal life, eventually develop seizures, and die before they reach weaning age, while hemizygous animals are phenotypically normal and have a normal life expectancy. Transgene expression in the central nervous system (CNS) has profound consequences for myelin formation and maintenance: approximately twofold overexpression of PLP/DM-20, as seen in homozygotes, results in apoptosis of mature, and a developmental arrest of the remaining immature oligodendrocytes. Severe dysmyelination ensues, associated with reactive astrogliosis and microglia activation/proliferation. Activation of microglia is also prominent in hemizygous rats with low levels of transgene overexpression. In these animals, myelin sheaths remain intact, but there is low-grade myelin degeneration throughout life witnessed by myelin uptake and activation of microglia and astrocytes, in the absence of the expression of major histocompatibility complex class II gene products. There were no spontaneous lymphocytic infiltrates in areas of myelin degeneration. However, hemizygous LEW.PLP rats were more sensitive to experimental autoimmune encephalomyelitis mediated by T cells specific for PLP, but not another encephalitogenic myelin protein, MBP.
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PMID:Transgenic Lewis rats overexpressing the proteolipid protein gene: myelin degeneration and its effect on T cell-mediated experimental autoimmune encephalomyelitis. 1037 78


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