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)

We demonstrated time course of the number of mononuclear cells (MNCs) isolated from spinal cords (SCs) correlates with the degree of experimental autoimmune encephalomyelitis (EAE) of Lewis rats, and analyzed their tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta production by MNCs, using enzyme-linked immuno sorbent assay and enzyme-linked immuno spot (ELISPOT) assay. The number of MNCs varied from 5 to 620 x 10(4) per SC of normal Lewis rat and Lewis rat with EAE. MNCs increased and reached a peak on day 2 post clinical onset (Day 2), and subsequently declined through the clinical course. The increase of infiltrating MNCs in SCs paralleled the severity of the disease development. TGF-beta 1 in plasma of rats with EAE significantly increased on Day 1 and reached the peak on Day 3. TNF-alpha levels in culture supernatants of MNCs from SCs increased on Day 1, and it decreased from Day 2, and declined on Day 4 when animals began to recover. TGF-beta 1 was not detected in culture supernatant during the whole clinical course. The number of TNF-alpha and TGF-beta 1 producing cells that were detected by ELISPOT assay increased on Day 0, and decreased rapidly after the onset of neurological symptoms. Thus, increase of TNF-alpha appeared in the early phase of the disease and then promptly decreased. In contrast, TGF-beta 1 was activated during the later recovering phase of the disease. We consider that TNF-alpha may play an important role in the pathogenesis of EAE and TGF-beta may inhibit the development of EAE.
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PMID:Tumor necrosis factor-alpha and transforming growth factor-beta production by isolated mononuclear cells from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis. 952 3

An immunodominant epitope of myelin basic protein (MBP), VHFFKNIVTPRTP (p87-99), is a major target of T cells in brain lesions of multiple sclerosis (MS), and this peptide can trigger experimental autoimmune encephalomyelitis (EAE). We designed truncated peptides based on this pathogenic 13-mer that are not antigenic. These short peptides reduced production of IFN-gamma and TNF-alpha in vivo. Moreover, paraplegic rats given the 7-mer FKNIVTP in soluble form showed total reversal of paralysis in 24 h. Truncated peptides that are too small to stimulate antigenic responses to pathogenic regions of myelin basic protein are nevertheless effective tolerogens and are able to anergize autoreactive T cells. Short peptide-based tolerogens, devoid of immunogenic and pathogenic potential, may be attractive for therapy of autoimmune diseases.
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PMID:Short peptide-based tolerogens without self-antigenic or pathogenic activity reverse autoimmune disease. 959 Feb 72

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

Normal human IgG for intravenous use (IVIg), administered intraperitoneally, protected Lewis rats against experimental allergic encephalomyelitis (EAE) induced by immunization with myelin basic protein (MBP). We demonstrate that protection was associated with an acquired unresponsiveness of lymphocytes to MBP and a decreased ability of the cells to produce IL-2, IFN-gamma and TNF-alpha and, to a lesser degree, IL-4 and IL-10, in the presence of the antigen. Lymph node (LN) cells of protected rats failed to passively transfer EAE to naive syngeneic animals. Our observations indicate that, rather than inducing selective immune deviation, IVIg induces preferential MBP unresponsiveness of Th1 cells. Whereas LN and splenic cells of IVIg-treated rats did not proliferate nor secrete IL-2 in the presence of the antigen, proliferation was restored by adding exogeneous recombinant IL-2. In contrast, LN cells of IVIg-treated rats proliferated normally and produced IL-2 in the presence of concanavalin A, indicating the selectivity for MBP of the anergy induced by IVIg when given at the time of immunization with the antigen. Treatment with IVIg also allowed a resistance to the secondary induction of EAE, indicating that IVIg protects from EAE but does not interfere with the processes that eventually lead to resistance to re-challenge. These data document the immunomodulatory effects of IVIg in T cell-dependent experimental autoimmune disease and further suggest a role for normal Ig in the selection of functional T cell repertoires.
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PMID:Normal immunoglobulin G protects against experimental allergic encephalomyelitis by inducing transferable T cell unresponsiveness to myelin basic protein. 964 63

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions may result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86) were also expressed, but to a lower extent, while B7-1 (CD80) expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative levels rather than sequential expression of Th1- and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention.
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PMID:Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus). 965 70

Autoimmunity and oxidative/excitotoxic damage are considered as possible pathogenetic mechanisms in amyotrophic lateral sclerosis (ALS). As tumor necrosis factor (TNF) is implicated in autoimmune diseases, including experimental autoimmune encephalomyelitis, and can be neurotoxic, we studied TNF production in a proposed animal model of ALS, the mnd mouse. These mice develop symptoms (progressive weakness of the limbs) as late as at 7 months of age. We measured TNF in serum, brain and spinal cord of mnd mice at 3 and 7 months of age. TNF was detectable in the brain and spinal cord (but not in the serum) at 7 months, while no TNF was detected in mnd mice at 3 months (asymptomatic) or in control mice of the same genetic background and the same age. Immunohistochemistry confirmed localization of TNF-alpha in motor neurons situated in the ventral horn of the spinal cord of 7-month old mnd mice. These results suggest the possibility of testing inhibitors of TNF production in this disease.
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PMID:Tumor necrosis factor is increased in the spinal cord of an animal model of motor neuron degeneration. 968 89

We studied the kinetics of expression of costimulatory molecules and cytokines in the central nervous system (CNS) in murine relapsing experimental autoimmune encephalomyelitis (EAE). During the natural course of EAE, B7-2 expression in the CNS correlated with clinical signs, while B7-1 was exclusively expressed during remissions. Interestingly, B7-1 was expressed on infiltrating mononuclear cells as well as neuronal cells in the CNS. In the periphery, B7-1 expression on APCs peaked with clinical disease but decreased on T cells. CD28 and CTLA4 molecules, the two known ligands for B7-1 and B7-2, had distinct expression patterns in the CNS; CD28 was highly expressed and correlated with B7-2 expression on APCs (macrophages/microglia as well as astrocytes) and with the clinical signs of EAE. CTLA4, on the other hand, was expressed by substantially fewer cells during the effector phase of disease and peaked during remission, which is consistent with the emerging role of this molecule in the termination of immune responses. The expression of CD40 and CD40L in the CNS was increased during clinical attacks. The expression of IL-12, IFN-gamma, and TNF-alpha correlated with disease activity and severity, while TGF-beta was the only factor that was up-regulated during the recovery phase. Interestingly, TGF-beta was also expressed by neurons during remission. This is the first study demonstrating the kinetics of the in vivo expression of costimulatory molecules, their ligands, and cytokines in an autoimmune disease model characterized by remissions and relapses. Our data suggest that the targeting of costimulatory molecules to block an immune response must take into account the expression patterns in the target organ.
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PMID:Kinetics of expression of costimulatory molecules and their ligands in murine relapsing experimental autoimmune encephalomyelitis in vivo. 968 68

To elucidate the efficacy of 4-acetylaminophenylacetic acid (actarit), an anti-rheumatic drug, on neuroinflammatory diseases such as multiple sclerosis, the effects of actarit on both actively induced and adoptively transferred experimental autoimmune encephalomyelitis (EAE) were studied. Daily intraperitoneal administration of actarit during the effector phase of active EAE and transferred EAE suppressed the clinical manifestation and pathological findings of EAE at doses of 300 mg/kg or higher. The percentages of CD4 and CD25 positive cells in the infiltrating cells in the CNS were reduced by this treatment. Semi-quantitative cytokine analysis revealed that the mRNA expression of TNF-alpha and INF-gamma in spinal cords and spleens of actarit treated active EAE rats was significantly reduced compared with vehicle treated EAE rats. The mRNA expression of IL-10 on day 17 in spleens of actarit-treated EAE rats was significantly upregulated. Actarit is potentially useful for the treatment of neuroimmunological disorders, such as multiple sclerosis.
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PMID:Suppressive effects of 4-acetylaminophenylacetic acid (actarit) on experimental autoimmune encephalomyelitis in rats. 971 59

To examine the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of degenerative disorders of the central nervous system (CNS), transgenic mice were developed in which expression of murine TNF-alpha was targeted to astrocytes using a glial fibrillary acidic protein (GFAP)-TNF-alpha fusion gene. In two independent GFAP-TNFalpha transgenic lines (termed GT-8 or GT-2) adult (>4 months of age) animals developed a progressive ataxia (GT-8) or total paralysis affecting the lower body (GT-2). Symptomatic mice had prominent meningoencephalitis (GT-8) or encephalomyelitis (GT-2) in which large numbers of B cells and CD4+ and CD8+ T cells accumulated at predominantly perivascular sites. The majority of these lymphocytes displayed a memory cell phenotype (CD44high, CD62Llow, CD25-) and expressed an early activation marker (CD69). Parenchymal lesions contained mostly CD45+ high, MHC class II+, and Mac-1+ cells of the macrophage microglial lineage with lower numbers of neutrophils and few CD4+ and CD8+ T cells. Cerebral expression of the cellular adhesion molecules ICAM-1, VCAM-1, and MAdCAM as well as a number of alpha- and beta-chemokines was induced or upregulated and preceded the development of inflammation, suggesting an important signaling role for these molecules in the CNS leukocyte migration. Degenerative changes in the CNS of the GFAP-TNFalpha mice paralleled the development of the inflammatory lesions and included primary and secondary demyelination and neurodegeneration. Disease exacerbation with more extensive inflammatory lesions that contained activated cells of the macrophage/microglial lineage occurred in GFAP-TNFalpha mice with severe combined immune deficiency. Thus, persistent astrocyte expression of murine TNF-alpha in the CNS induces a late-onset chronic inflammatory encephalopathy in which macrophage/microglial cells but not lymphocytes play a central role in mediating injury.
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PMID:Late-onset chronic inflammatory encephalopathy in immune-competent and severe combined immune-deficient (SCID) mice with astrocyte-targeted expression of tumor necrosis factor. 973 27

Experimental autoimmune encephalomyelitis (EAE) and other organ-specific autoimmune diseases are induced by autoantigen-specific Th1 cells. In contrast, transfer of autoantigen-reactive Th2 cells that produce IL-4 and IL-10 can prevent and/or reverse EAE. The relative roles of these two Th2 cytokines in the regulation of EAE has not been evaluated. Utilizing IL-4 and IL-10 knockout mice deficient for these cytokines and IL-10 and IL-4 transgenic mice overexpressing these cytokines, we demonstrate that IL-10-deficient mice (IL-10(-/-)) are more susceptible and develop a more severe EAE when compared with IL-4-deficient mice (IL-4(-/-)) or wild-type mice. T cells from IL-10(-/-) mice exhibit a stronger Ag-specific proliferation, produce more proinflammatory cytokines (IFN-gamma and TNF-alpha) when stimulated with an encephalitogenic peptide, and induce very severe EAE upon transfer into wild-type mice. In contrast, while IL-4 transgenic mice develop similar disease compared with their nontransgenic littermates, mice transgenic for IL-10 are completely resistant to the development of EAE. Taken together, our data suggest that IL-10 plays a more critical role in the regulation of EAE by regulating autopathogenic Th1 responses.
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PMID:IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. 975 45


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