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)

Human interferon-beta (human IFN-beta) and rat interferon (rat IFN) were evaluated on experimental allergic encephalomyelitis (EAE) in rats, a delayed cellular reaction resembling human multiple sclerosis (MS). Rat IFN was active by intravenous and intracerebroventricular routes. It decreased the severity of clinical symptoms of paralysis during the 22 days of the assay. Human IFN-beta, on the contrary, had no effect when similarly tested in this rat model. Cyclophosphamide delayed the onset of paralysis, but levamisole enhanced the severity of the EAE.
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PMID:Effect of rat and beta-human interferons on hyperacute experimental allergic encephalomyelitis in rats. 241 42

The objective of this study was to compare the sensitivity of 11 porcine viruses to the antiviral effects of porcine interferon-alpha in serum from piglets which had been infected 19 h previously with transmissible gastroenteritis virus, and of porcine interferon-beta prepared in PK-15 cells by induction with polyinosinic:polycytidylic acid, in yield reduction assays in pig kidney cells which were treated with interferon before virus challenge, and both before and after virus challenge. The most sensitive virus to both types of interferon was vesicular stomatitis. A porcine isolate of bovine herpesvirus type 1, hemagglutinating encephalomyelitis virus and porcine enterovirus types 1 and 2 were also highly sensitive to interferon-alpha. There was little reduction in the yield of porcine parvovirus or porcine rotavirus, while swinepox, swine influenza and transmissible gastroenteritis viruses were intermediate in their sensitivity to interferon-alpha. In addition to vesicular stomatitis virus, porcine adenovirus type 3, swine influenza, hemagglutinating encephalomyelitis and porcine rotavirus were highly sensitive to interferon-beta, while swinepox, bovine herpesvirus type 1, porcine parvovirus, transmissible gastroenteritis and porcine enteroviruses were less sensitive than the above viruses to interferon-beta, although all showed significant reductions in virus yield.
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PMID:The interferon sensitivity of selected porcine viruses. 249 45

The results of two phase III clinical trials have recently shown that interferon-beta (IFNbeta) is effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Treatment with IFNbeta results in a significant decrease in the rate of clinical relapse and a marked delay in progression to disability compared to placebo-treated control patients. In the present study, we demonstrate similar therapeutic effects after treating (SWR X SJL)F1 mice with IFNbeta at the onset of clinical signs of experimental autoimmune encephalomyelitis (EAE), a disease animal model widely used in MS studies. EAE was actively induced by immunization of (SWR X SJL)F1 mice with the immunodominant encephalitogenic peptide 139-151 of myelin proteolipid protein (PLP). In blinded testing, mice treated with IFNbeta at EAE onset showed a delay in progression to clinical disability as determined by marked improvement with time in mean clinical score, significant delay in onset of relapse, and significant decrease in exacerbation frequency compared to placebo-treated control mice. The therapeutic effect of IFNbeta was accompanied by a significant inhibition of delayed-type hypersensitivity (DTH) but not proliferation in response to the priming PLP 139-151. In addition, IFNbeta treatment resulted in an overall decrease in severity of both inflammation and demyelination in the central nervous system. These results mimic in an autoimmune animal model the effectiveness of IFNbeta treatment observed in MS. Moreover, our study suggests that anti-viral properties of IFNbeta are not essential for producing therapeutic effects in autoimmune demyelinating disease, and that the efficacy of IFNbeta in the treatment of MS may be due to inhibition of autoreactivity.
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PMID:Interferon-beta inhibits progression of relapsing-remitting experimental autoimmune encephalomyelitis. 859 95

Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system (CNS) principally in young adults. Although its etiology is as yet unknown current evidence suggests that tissue damage is mediated by autoimmune T cells. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), has demonstrated that myelin basic protein (MBP)- or proteolipid protein (PLP)-specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE have shown that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon-gamma and tumor necrosis factor-alpha/beta. Understanding the pathogenetic steps in lesion development at the molecular level led to highly specific immunotherapies for EAE targeting each individual molecule. It has been the hope of many investigators that immunological events resembling those in EAE can be found in patients with MS and that the specific immunotherapies effective in EAE could also be applied to MS. However, to date, the evidence for a unique immunological abnormality in MS is not strong. Although MBP- and PLP-specific T cells with properties similar to those that are encephalitogenic in animals can be isolated from patients, they are not specific for MS and occur with similar frequency in controls. In addition, the variability in specificity and TCR usage has raised questions regarding the relevance of these cells in patients. The importance of the T cell responses to myelin antigens in MS may not be established until the effects of abrogating their activity through specific therapies targeting the trimolecular complex (TMC) have been demonstrated. Consequently, attention has begun to focus on modifying the biology of the MS lesion rather than targeting the initiating event at the level of the TMC, and the success of this approach is reflected by the effect of interferon-beta on lesion development in MS. The recent approval for the use of interferon-beta for the treatment of relapsing-remitting MS has raised great interest in examining novel strategies for immunotherapies in MS. The basic concepts as well as the current candidates for such new immunotherapies will be outlined in this short review.
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PMID:Experimental immunotherapies for multiple sclerosis. 898 75

The etiology of multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), is not yet known. Immunological, clinical and pathological studies suggest, however, that T lymphocytes directed against myelin antigens are involved in the pathogenesis of MS. The examination of an experimental animal model for MS, experimental allergic encephalomyelitis (EAE), demonstrated that myelin basic protein-(MBP) or proteolipidprotein-(PLP) specific T cells mediate the destruction of CNS myelin. In recent years, elegant studies in EAE showed that encephalitogenic T cells recognize short peptides of MBP or PLP in the context of MHC/HLA-class II molecules, express a restricted number of T cell receptor (TCR) molecules and secrete interferon-gamma and tumor necrosis factor-alpha/beta. Understanding the pathogenetic steps of demyelination at the molecular level led to highly specific immunotherapies of EAE targeting each individual molecule. MBP- and PLP-specific T cells with similar properties could also be isolated from MS patients and control individuals. Due to their heterogeneity in terms of specificity, function and TCR usage, it was difficult, however, to draw definite conclusions from these results, so far. The recent approval of interferon-beta, a cytokine that antagonizes a number of the effects of interferon-gamma, for the treatment of MS has raised great interest in examining novel strategies for immunotherapies in MS. The basic concepts as well as the current candidates for such new immunotherapies will be outlined in this brief article.
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PMID:Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis and their application for new therapeutic strategies. 926 14

Early pregnancy factor (EPF) is a secreted protein with immunosuppressive and growth factor properties. During pregnancy, it appears in maternal serum within 6-24 h of fertilization, is present for at least the first two-thirds of pregnancy in all species studied and is essential for embryonic survival. It is a homologue of chaperonin 10, a heat shock protein, but, unlike other members of this family, EPF has an extracellular role. As it has the ability to modulate CD4+ T cell-dependent immune responses, its role in treatment of experimental autoimmune encephalomyelitis (EAE) was investigated. EAE is a CD4+ T cell-mediated disease, the best available animal model of multiple sclerosis (MS). Two models of EAE were investigated, acute EAE induced in Lewis rats by inoculation with myelin basic protein (MBP-EAE) and chronic relapsing EAE induced in SJL/J mice by inoculation with myelin proteolipid protein peptide (residues 139-151) (PLP-EAE). EPF, delivered intraperitoneally or orally to rats or intraperitoneally to mice, suppressed clinical signs of disease. Mice with PLP-EAE were also treated with interferon-beta, with and without EPF. Both EPF and IFN-beta suppressed clinical signs of EAE and, when administered together, gave greater suppression than when given separately. These findings suggest that EPF may be a potential candidate for use in treatment of MS and may be of use in combined therapy with IFN-beta.
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PMID:Early pregnancy factor suppresses experimental autoimmune encephalomyelitis induced in Lewis rats with myelin basic protein and in SJL/J mice with myelin proteolipid protein peptide 139-151. 1110 34

Glatiramer acetate (Copaxone) is a novel preparation of synthetic peptides composed of four amino acids. Laboratory studies have shown that it prevents, or modifies, experimental allergic encephalomyelitis, the animal model for multiple sclerosis (MS), in several mammalian species. Its mode of action has not been fully elucidated but it is known to induce suppresser T-cells, known to be deficient in MS, and competitively inhibits the effect of CNS myelin antigens, thought to be important in the pathogenesis of MS, through MHC blockade. Controlled clinical trials have shown it to improve the natural history of MS by reducing both the relapse rate and the resultant disability. GA shows similar efficacy to interferon-beta (IFN-beta) but with fewer systemic side-effects and appears to be better tolerated by patients. It has thus justified its place in the new era of disease-modifying treatments for MS. While the evidence suggests GA should be considered as first-line therapy in selected patients, its differing mechanism of action also gives patients and doctors the option of an alternative agent when the efficacy of IFN-beta is waning or side-effects predominate.
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PMID:Glatiramer acetate (Copaxone). 1150 Dec 29

Interleukin-12 is critical to the pathogenesis of experimental autoimmune encephalomyelitis in multiple species. Interleukin-10, a dominant endogenous inhibitor of interleukin-12, is largely protective in these experimental surrogates for multiple sclerosis. Such data have suggested that an interleukin-12/interleukin-10 immunoregulatory circuit is a key determinant of disease expression in experimental autoimmune encephalomyelitis. For multiple sclerosis itself, compatible cytokine data have been reported. The mechanisms underlying the beneficial effects of interferon-beta in multiple sclerosis remain unclear, hampering the search for more effective therapies. Of note, interferon-beta has reciprocal effects on these cytokines in vitro, suppressing interleukin-12 and augmenting interleukin-10 production. To examine the effects of interferon-beta on the interleukin-12/interleukin-10 axis in multiple sclerosis, we characterized the production of these cytokines by peripheral blood mononuclear cells from patients beginning therapy with interferon-beta. Before therapy, multiple sclerosis patients exhibited increased stimulatable interleukin-12 production compared with controls. Interferon-beta therapy leads to inhibition of interleukin-12 and augmentation of interleukin-10 production, significantly elevating the ratio of secreted interleukin-10 to interleukin-12. These effects, observed equally in patients with relapsing-remitting and progressive disease, indicate that interferon-beta affects the interleukin-12/interleukin-10 axis in ways thought to be beneficial to multiple sclerosis patients. More specific therapeutic targeting of these pathways may be warranted.
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PMID:Interferon-beta therapy for multiple sclerosis induces reciprocal changes in interleukin-12 and interleukin-10 production. 1183 72

Interferon-beta (IFN-beta) has beneficial effects on the clinical symptoms of multiple sclerosis (MS) patients, but its exact mechanism of action is yet unknown. We here suggest that IFN-beta directly modulates inflammatory events at the level of cerebral endothelium. IFN-beta treatment resulted in a marked reduction of perivascular infiltrates in acute experimental allergic encephalomyelitis (EAE), the rat model for MS, which was coupled to a major decrease in the expression of the adhesion molecules ICAM-1 and VCAM-1 on brain capillaries. In vitro, IFN-beta reduced the mRNA levels and protein expression of adhesion molecules of brain endothelial cell cultures and diminished monocyte transendothelial migration. Monocyte adhesion and subsequent migration was found to be predominantly regulated by VCAM-1. These data indicate that IFN-beta exerts direct antiinflammatory effects on brain endothelial cells thereby contributing to reduced lesion formation as observed in MS patients.
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PMID:Interferon-beta directly influences monocyte infiltration into the central nervous system. 1204 77

Nitric oxide (NO) has been implicated in the etiopathology of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), and inhibition of NO synthesis has been proposed to be a possible mechanism of action of drugs to treat MS. In the present study, we investigated the inhibitory effect on NO synthesis of various steroids, cytokines and drugs used or proposed for the treatment of MS. As a model system, we used primary rat microglial cells which produce NO synthase and subsequently release NO upon stimulation with lipopolysaccharide (LPS). Among the substances tested, the glucocorticoids prednisone, hydrocortisone, dexamethasone and progesterone as well as transforming growth factor-beta (TGF-beta) dose-dependently inhibited LPS-induced nitric oxide synthase (iNOS) and NO synthesis. In contrast, COP-1, the phosphodiesterase inhibitors rolipram and pentoxifylline, the cytokines interleukin-10 (IL-10) and interferon-beta (IFN-beta) as well as the steroids beta-estradiol, testosterone, and dehydroepiandrosterone (DHEA) showed no inhibitory effect. Cholesterol slightly, but not significantly, increased LPS-induced nitric oxide synthesis. We conclude from the present study that with respect to treatment of MS, inhibition of NO synthesis may be an important mechanism of action of glucocorticoids and transforming growth factor-beta, but not of other drugs used or proposed to treat MS.
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PMID:Inhibition of LPS-induced iNOS and NO synthesis in primary rat microglial cells. 1242 93


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