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)

Monocyte chemoattractant protein-1 (MCP-1), formerly termed JE, is a member of the beta-chemokine (C-C chemokine) family and has been shown to be produced by a variety of cell types. Recently, mRNA of JE/MCP-1 was detected in astrocytes during the acute phase of experimental allergic encephalomyelitis (EAE). In addition, supernatants collected from human cultured astrocytes have recently been found to be chemotactic for monocytes. However, chemokine production and function in glial cells has not been fully examined. Using a sandwich ELISA assay, we have now quantitated MCP-1 levels and assessed MCP-1 function on murine glial cells. Lipopolysaccharide (LPS), interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha induced MCP-1 secretion by astrocytes, but not microglia. In addition, pretreatment with interferon (IFN)-gamma significantly augmented MCP-1 production by either LPS or the above cytokines. In contrast, LPS preferentially induced production of another beta-chemokine, macrophage inflammatory protein-1 alpha (MIP-1 alpha) from microglial cells. MCP-1 induced chemotaxis of microglial cells and macrophages. Similarly, another beta-chemokine, TCA3, which is produced by encephalitogenic T lymphocytes, also induced chemotaxis of microglia and macrophages. These findings suggested that astrocytes and microglial cells differentially produce chemokines in the central nervous system, and that both astrocytes and T cells may facilitate recruitment and activation of microglial cells via production of beta-chemokines.
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PMID:Production and function of monocyte chemoattractant protein-1 and other beta-chemokines in murine glial cells. 764 42

The interferons (IFNs) are a family of secretory glycoproteins possessing potent antiviral, antiproliferative, antimicrobial, and immunomodulatory activities. It has been shown that the IFNs and superantigens have an important effect on the course of certain autoimmune disorders, and thus we have examined the effect of the type I and type II IFNs on superantigen-induced stimulation. The type I IFNs, alpha, beta, and tau, inhibited induction of T cell proliferation by several staphylococcal enterotoxin superantigens; the type II IFN, gamma, was without effect. The type I IFNs inhibited T cell proliferation to the same extent, approximately 50% at 10(3) units of IFN/ml, and in a dose-dependent manner. Consistent with inhibition of proliferation, the type I IFNs also inhibited IL-2 production as well as levels of IL-2 receptor expression. Inhibition was not increased by using the IFNs in combination, suggesting that they inhibited proliferation by the same mechanism. IFNs alpha and beta, but not IFN-tau, were toxic to cells at high concentrations (> or = 10(4) units/ml). Thus, the mechanism by which type I IFNs inhibit cell proliferation differs from that associated with their toxic effects. A partial reduction of V beta-specific superantigen-induced T cell expansion by type I IFNs was also demonstrated using flow cytometry. We recently showed that superantigens play an important role in the reactivation of experimental allergic encephalomyelitis. The potent antiproliferative activities of the type I IFNs strongly suggest the further study of their use as therapies for superantigen-associated diseases, such as multiple sclerosis and other autoimmune disorders, as well as toxic shock syndrome.
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PMID:Type I interferon inhibition of superantigen stimulation: implications for treatment of superantigen-associated disease. 764 33

The lymphokine production of two T-cell clones, which both recognize epitopes within the encephalitogenic 139-151 sequence of myelin proteolipid protein, was examined after stimulation with immobilized antibodies to the CD3 moiety of the T-cell-receptor complex. Clone A1 produced interleukin (IL)-2 and interferon (IFN)-gamma, but no IL-4, while clone D5 produced IL-4, but no IL-2 or IFN-gamma. A1 therefore belongs to the T-helper type 1 (Th1) subset, while D5 is a Th2 clone. In addition, the Th1 clone induced severe experimental allergic encephalomyelitis (EAE), while the Th2 clone did not induce any signs of EAE. Synthetic peptides were used to demonstrate that these clones recognized slightly different epitopes within the 139-151 sequence. Histidine 139 was shown to be optimal for the stimulation of the Th2 clone, while the presence of this residue inhibited the stimulation of the Th1 clone. Th2 cells specific for an encephalitogenic peptide may be important in the regulation of encephalitogenic Th1 cells.
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PMID:Fine-specificity differences in the recognition of an encephalitogenic peptide by T helper 1 and 2 cells. 769 54

Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I-restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H-2 Kb molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma-interferon (IFN-gamma) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction.
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PMID:Effect of persistent mouse hepatitis virus infection on MHC class I expression in murine astrocytes. 771 17

The Daniels strain of Theiler's virus causes a persistent infection of the white matter of spinal cord of susceptible mice, with chronic inflammation and primary demyelination. Inbred 129Sv mice are resistant to this infection; they present with mild encephalomyelitis and clear the infection within a matter of days. A very different outcome was observed with inbred 129Sv mice whose receptors for interferon alpha/beta or interferon gamma had been inactivated by homologous recombination. The former presented severe encephalomyelitis with acute infection of neurons, particularly in brain and hippocampus, and extensive infection with necrosis of the choroid plexus. Most animals died of this acute disease. The latter, presented the same early encephalomyelitis as the control 129Sv mice. However, they remained persistently infected and developed a very severe late infection of the white matter with extensive primary demyelination. This late disease looked like an exacerbated form of the chronic demyelinating disease observed in susceptible inbred mice such as the SJL/J or FVB strains. Our results show that the two interferon systems play nonredundant roles in the resistance of the 129Sv mouse to the infection by Theiler's virus. They also lend support to the notion that the Ifg gene is involved in the resistance/susceptibility of inbred strains of mice to persistent infection by this picornavirus.
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PMID:Theiler's virus infection of 129Sv mice that lack the interferon alpha/beta or interferon gamma receptors. 775 99

In vitro experiments using purified rat CD4+ T cells in primary and secondary mixed leukocyte cultures (MLC) have been carried out to explore the mechanism of inhibition of cell-mediated autoimmune disease in the rat by a nondepleting monoclonal antibody (mAb) to CD4. Previous work has shown that W3/25, a mouse anti-rat CD4 mAb of immunoglobulin G1 isotype, completely prevents the development of the paralysis associated with experimental allergic encephalomyelitis (EAE) in Lewis rats, but does so without eliminating the encephalitogenic T cells. The in vitro experiments described in this study have shown that when CD4+ T cells were activated in the presence of the anti-CD4 mAb in a primary MLC, the synthesis of interferon (IFN) gamma, but not interleukin (IL) 2, was completely inhibited. After secondary stimulation, now in the absence of the mAb, the synthesis of IL-4 and IL-13 mRNA was greatly enhanced compared with that observed from CD4+ T cells derived from primary cultures in which the mAb was omitted. As IL-4 and IL-13 are known to antagonize cell-mediated immune reactions, and as EAE is cell-mediated disease, the data suggest that the W3/25 mAb controls EAE by modifying the cytokine repertoire of T cells that respond to the encephalitogen. The capacity for the mAb to suppress IFN-gamma synthesis provides, in part, an explanation for this change in cytokine production. These findings are discussed in terms of what is known of the factors that determine which cytokine genes are expressed on T cell activation. Possible implications for the evolution of T cell responses in human immunodeficiency virus infection are also discussed.
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PMID:Activation of CD4+ T cells in the presence of a nondepleting monoclonal antibody to CD4 induces a Th2-type response in vitro. 779 Aug 23

Intracerebral (i.c.) inoculation of susceptible strains of mice with Theiler's murine encephalomyelitis virus (TMEV) results in immune-mediated demyelination. We examined the role of interferon (IFN)-gamma in this virally induced pathogenesis. Intraperitoneal (i.p.) injection of susceptible mice with an IFN-gamma-neutralizing monoclonal antibody (mAb), DB-1, resulted in a significantly accelerated onset of disease. The anti-IFN-gamma mAb-treated animals showed a strong delayed-type hypersensitivity (DTH) response to the virus similar to that of control mAb-treated animals. Treatment with anti-IFN-gamma mAb had no significant effect on the clinical course of disease. However, intracerebral administration of recombinant IFN-gamma significantly accelerated the onset of TMEV-induced disease, as well as enhanced TMEV-specific T cell proliferation and DTH responses. The enhancing effect of IFN-gamma was completely abrogated by simultaneous treatment with anti-IFN-gamma mAb. Collectively, our data suggest that the level of IFN-gamma plays a key role in the TMEV-induced inflammatory response and a perturbation of this balance may result in an alteration in the course of the demyelinating disease.
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PMID:Alteration in the level of interferon-gamma results in acceleration of Theiler's virus-induced demyelinating disease. 782 64

Induction of experimental allergic encephalomyelitis is facilitated in a genetically resistant BALB/c mouse strain by a nonpathogenic strain of a neurotropic alphavirus, Semliki Forest virus (SFV-A7). One possible explanation for this enhancement is virus infection of endothelial cells (EC), causing increased permeability of the blood-brain barrier. We have now sought evidence for virus infection of EC in vivo by immunocytochemistry and in situ hybridization. SFV-A7 antigens and RNA were detected in vascular EC and perivascular neurons in cerebellar and spinal cord white matter. Expression of viral antigens was followed by fibrinogen leakage from the blood vessels into brain parenchyma. This was shown by immunoperoxidase staining detecting fibrinogen extravascularly in central nervous system sections of infected mice. Simultaneously, expression of ICAM-1 (intercellular adhesion molecule 1) was induced on brain EC. SFV-A7 replicated in mouse brain microvascular EC in vitro and caused lysis of the cells. SFV-A7 did not induce ICAM-1 expression of mouse brain microvascular EC in vitro, while ICAM-1 was readily induced by gamma interferon and interleukin 1 beta. The observed increase of ICAM-1 expression on EC is immune mediated and not a direct effect of the virus infection. We conclude that SFV-A7 infection causes cerebral microvascular damage which contributes to the facilitation of experimental allergic encephalomyelitis in BALB/c mice.
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PMID:Semliki Forest virus infects mouse brain endothelial cells and causes blood-brain barrier damage. 791 58

The intravenous infection of Theiler's virus GD VII strain causes acute encephalomyelitis in infected mice. To determine the cellular mechanism of resistance and interferon (IFN)-gamma-producing cell populations, mononuclear cells isolated from tissues of the brain were analyzed by the flow cytometry method. Antibodies specific for CD3, CD4, CD8, T cell receptor (TCR)-alpha beta, and Asialo GM1 were used to deplete the corresponding cell populations in Theiler's virus-infected mice. CD4+ lymphocytes and CD8+ lymphocytes infiltrated in the brains of infected mice from 5 days postinfection (p.i.). The number of CD3+/TCR-gamma delta+ lymphocytes increased in the brains on Day 6 p.i. The elimination of CD3+ lymphocytes or CD4+ lymphocytes augmented viral replication and suppressed the production of IFN-gamma. The suppression of IFN-gamma production by anti-CD3 monoclonal antibody (mAb) persisted, although the suppression by anti-CD4 mAb was observed only on Day 6 p.i. The depletion of CD8+ lymphocytes as well as TCR-alpha beta+ lymphocytes also augmented the viral replication; however, it did not alter the production of IFN-gamma. Anti-Asialo GM1 antibody had no effect on viral replication and IFN-gamma production. These results indicate that T lymphocytes are important for eliminating Theiler's virus from the brain, CD3+/CD4+/CD8- lymphocytes and CD3+/TCR alpha beta-/CD4-/CD8- lymphocytes would produce IFN-gamma in brain. However, from the result on the experiment of the depletion of TCR-alpha beta+ lymphocytes, the defence mechanisms by T lymphocytes against Theiler's virus would be independent of endogenous IFN-gamma production.
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PMID:Theiler's virus is eliminated by a gamma-interferon-independent mechanism in the brain. 820 21

We induced a chronic relapsing form of experimental autoimmune encephalomyelitis in 7- to 10-week-old female SJL/J mice using a subcutaneous injection of an emulsion containing syngeneic mouse spinal cord homogenate in phosphate-buffered saline and Mycobacterium tuberculosis (MT) in incomplete Freund's adjuvant. Following the animals' recovery from the first attack periods, we fed them varying doses of type I interferon (IFN) or mock IFN three times per week for 6 weeks. This treatment decreased proliferation to guinea pig myelin basic protein and MT compared with control in draining lymph node and diminished inflammation in the CNS. Oral IFN altered the cytokine profile of concanavalin A-activated spleen cells by decreasing IFN-gamma secretion. These results suggest that type I IFNs are active by the oral route, have significant clinical and immunomodulatory effects, and can decrease an established and ongoing immune response to sensitized antigens. The oral administration of biologic-response modifiers, such as type I IFNs, provides a potentially nontoxic, convenient, continuous means of delivering immunoactive substances via the gut regional immune system that can alter cytokine production and suppress clinical relapses.
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PMID:Suppression of relapsing experimental autoimmune encephalomyelitis in the SJL/J mouse by oral administration of type I interferons. 820 13


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