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 allergic encephalomyelitis (EAE) was generated in SJL and B10.PL mice by using the synthetic myelin basic protein peptides. Inflammation in brain and spinal cord preceded clinical signs of disease. Infiltrating lymphocytes were predominantly Lyt1+ (CD5+), L3T4+ (CD4+) T cells, until day 18. After that, F4/80+ monocyte/macrophages outnumbered T cells. Ia+ cells were microglia, macrophages, and endothelial cells, but Ia was not detectable on astrocytes in this EAE model. Ia+ endothelial cells appeared later in the disease than Ia+ microglia and macrophages, suggesting that antigen presentation at the blood-brain barrier is not initially responsible for inflammation. Cells staining for interferon gamma, interleukin 2 (IL-2), and IL-2 receptors were more prominent than IL-4, IL-5, lymphotoxin (LT), and tumor necrosis factor alpha (TNF-alpha), which occurred transiently in the second week and were associated with fewer cells. TNF-alpha and LT were never seen in spinal cord, suggesting that these cytokines are not responsible for initiation of clinical disease. Few or no cells stained for IL-6, IL-1, or transforming growth factor beta. Control animals injected with complete Freund's adjuvant in saline or control antigen demonstrated no inflammatory cell infiltration or cytokine production. Thus, our findings suggest a peptide-induced EAE model in which Th1 T-cell-macrophage interactions result in the disease process.
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PMID:Inflammatory leukocytes and cytokines in the peptide-induced disease of experimental allergic encephalomyelitis in SJL and B10.PL mice. 137 May 83

Interleukins have been postulated to exert an important modulatory and recruiting role in the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination of the central nervous system (CNS) in SJL/J mice. Using bio- and radioimmunoassays, we have detected and quantified some of the interleukins suspected to play a role in this immune-mediated process. The interleukins 1 and 2 (IL-1, IL-2) and interferon-gamma (IFN-gamma) have been measured in homogenates from the CNS and sera from infected animals, as well as in supernatants from antigen-specific in vitro-stimulated spleen and meningeal cells. IL-1 was detected both in CNS tissue homogenates (approximately 20-40 fmol/ml) and in splenic cultures (200 U/ml). IL-2 was detected only after TMEV-specific antigenic stimulation in spleen cultures (approximately 120 U/ml). In vitro, IL-2 and IL-1 synthesis appear in a dose- and time-dependent manner. IFN-gamma could not be found in any case. The precise nature of IL-1 and IL-2 activity was further assessed by HPLC. The above results strongly indicate the presence of functionally active macrophages in the CNS infiltrates of cells triggering this autoaggressive immune process. In addition, we propose a central role for IL-1 in augmenting the intracerebral immune response leading to the inflammatory demyelination induced by TMEV.
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PMID:IL-1, IL-2 and IFN-gamma production by Theiler's virus-induced encephalomyelitic SJL/J mice. 174 75

To assess the role of IL-1 in the development of experimental autoimmune encephalomyelitis (EAE), the effects of in vivo treatment with IL-1 alpha or an IL-1 antagonist on the clinical course of EAE were evaluated. First, Lewis rats were immunized with guinea pig myelin in CFA and treated for 19 consecutive days with i.p. injections of recombinant human IL-1 alpha. Clinical signs of paralysis in the IL-1 alpha-treated groups were of longer duration and of greater severity compared to placebo injected controls. In addition, more weight loss was observed in the IL-1 alpha-treated groups compared to controls. This enhanced weight loss was not due to IL-1 alpha injections alone as CFA-treated rats injected with IL-1 alpha did not lose weight when compared to placebo injected, CFA-treated controls. Second, soluble mouse rIL-1R (sIL-1R), which binds both IL-1 alpha and IL-1 beta, was given as an IL-1 antagonist. Treatment of guinea pig myelin/CFA immunized rats with sIL-1R for 13 consecutive days significantly delayed the onset of EAE, reduced the severity of paralysis and weight loss, and shortened the duration of disease. Treatment with sIL-1R was most effective in reducing EAE if administered for 15 consecutive days immediately after immunization. Shortened 5-day treatment regimens spanning days 1 to 5, days 6 to 10, or days 11 to 15 after immunization were less effective in reducing EAE. These data suggest that IL-1 may initiate or promote inflammation within the central nervous system. In addition, specifically blocking the biological activity of IL-1 in vivo by soluble receptors may prove beneficial for the treatment of autoimmune or inflammatory diseases.
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PMID:Experimental autoimmune encephalomyelitis is exacerbated by IL-1 alpha and suppressed by soluble IL-1 receptor. 182 2

The immunomodulatory azaspirane SK&F 105685 has immunosuppressive activity in animal models of autoimmune disease such as adjuvant-induced arthritis and experimental autoimmune encephalomyelitis. The mechanism of SK&F 105685 appears to be the induction of nonspecific suppressor cell (SC) activity. SC appear to be "null cells," that is, cells that lack specific cell surface markers of mature B cells, T cells, natural killer (NK) cells, or macrophages. Because we hypothesized that the induction of SC was associated with enhanced hematopoiesis, we sought to determine the hematopoietic potential of SK&F 105685. Recombinant interleukin 1 alpha (rIL-1) was included as a positive control for hematopoietic stimulation in our studies. We demonstrate here that administration of SK&F 105685 increases the number of granulocyte-macrophage colony-forming units (CFU-GM) within the bone marrow 24 h after injection in a dose-dependent manner. In addition, the percentage of CFU-GM in S-phase of the cell cycle was significantly increased, as was colony-stimulating activity (CSA) present in the serum of treated animals. In our experiments IL-1 did not increase marrow CFU-GM; however, splenic CFU-GM, the proportion of CFU-GM in S-phase of the cell cycle, and serum CSA were all increased 24 h after a single treatment. Administration of SK&F 105685 24 h prior to lethal irradiation resulted in a dose-related increase in the number of surviving mice. These results demonstrate that SK&F 105685 and rIL-1 stimulate myelopoiesis in vivo and suggest a mechanism by which prophylactic treatment with these agents protects mice from otherwise lethal irradiation.
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PMID:Administration of an immunomodulatory azaspirane, SK&F 105685, or human recombinant interleukin 1 stimulates myelopoiesis and enhances survival from lethal irradiation in C57Bl/6 mice. 189 48

This investigation focused on the role of adherent accessory cells and their cellular product, interleukin 1 (IL 1), in cellular immune responses associated with experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Guinea pig myelin basic protein (GPMBP)-sensitized lymph node cells (LNC) responded in culture with GPMBP by undergoing activation as measured by augmented transfer of EAE to syngeneic recipients, and proliferation as measured by [3H]thymidine incorporation. GPMBP-sensitized LNC, after depletion of adherent accessory cells, no longer responded to GPMBP in the EAE transfer activation assay. In contrast, aliquots of the same LNC preparation exhibited proliferative responses to GPMBP that were only partially reduced. Addition of irradiated thymocytes to adherent cell-depleted cultures fully reconstituted responsiveness to GPMBP in the activation assay and restored full reactivity to GPMBP in the proliferation assay. Furthermore, addition of either purified human IL 1 or recombinant human IL 1 to adherent cell-depleted cultures reconstituted reactivity to GPMBP in the EAE transfer activation assay and augmented GPMBP-specific proliferative responses. Anti-Ia monoclonal antibodies blocked GPMBP + IL 1-induced cellular activation of nonadherent LNC. These results demonstrate that both IL 1 and Ia molecules are important in the pathway leading to GPMBP-induced activation of EAE-inducing T lymphocytes. Furthermore, these results suggest that different accessory signals may be required for optimal induction of GPMBP-induced lymphocyte activation vs GPMBP-specific proliferative responses.
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PMID:Interleukin 1 and myelin basic protein synergistically augment adoptive transfer activity of lymphocytes mediating experimental autoimmune encephalomyelitis in Lewis rats. 243 37

Cerebrospinal fluid (CSF) and plasma samples were taken from strain 13 guinea pigs in various stages of chronic relapsing experimental allergic encephalomyelitis (CREAE). The samples were assayed for interleukin 1 (IL-1) in the C3H/Hej mouse thymocyte assay. After removal of inhibitors, IL-1 was detectable in low amounts in plasma (5 U/ml) throughout the course of the disease but was raised in the acute phase (12 U/ml). CSF IL-1 was, however, only present in low amounts (6 U/ml) during the acute phase but was elevated (18 U/ml) during the chronic stages of CREAE. During the relapse phase levels of IL-1 correlated with the total leucocyte count in the CSF. On gel filtration of CSF, IL-1 activity eluted at approximately 15 kD and could not be attributed to leakage of plasma IL-1 during CSF puncture or IL-2 activity.
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PMID:Cerebrospinal fluid interleukin 1 like activity during chronic relapsing experimental allergic encephalomyelitis. 349 82

Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible strains, which clinically and histopathologically resembles human multiple sclerosis. Since bacterial LPS produced by Gram-negative bacteria is known to potentiate an immune response and trigger resident central nervous system cells to produce various inflammatory cytokines, we examined the ability of LPS to affect resistance to TMEV-induced demyelinating disease (TMEV-IDD). Intraperitoneal injection of LPS, concomitant with intracerebral of genetically resistant C57BL/6 mice with TMEV, resulted in clinical symptoms in approximately 50% of the group. The increase in susceptibility following LPS treatment correlated with the enhanced levels of TMEV-specific delayed-type hypersensitivity and T cell proliferative responses. Similar treatment with LPS, however, did not accelerate the clinical course of susceptible (SJL/J) or intermediately susceptible (C3H) mice. The LPS-treated C57BL/6 mice displayed an increased viral persistence in the central nervous system when compared with nontreated control mice. Intraperitoneal administration of IL-1 beta could mimic the LPS effect in C57BL/6 mice, suggesting that the increase in susceptibility to TMEV-IDD may function via IL-1 produced following LPS stimulation.
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PMID:Treatment with bacterial LPS renders genetically resistant C57BL/6 mice susceptible to Theiler's virus-induced demyelinating disease. 759 13

Sindbis virus (SV) causes an acute encephalomyelitis in mice. A T cell-dependent inflammatory response is first detected 3 days after infection and includes T cells, B cells, and macrophages. The cytokines produced locally by intrinsic cells of the brain in response to infection and by infiltrating mononuclear cells and their contributions to outcome of infection have not been identified. Semiquantitative reverse transcriptase-PCR was used to evaluate the expression of mRNAs for IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, leukemia inhibitory factor (LIF), and TGF-beta in the brain during fatal and nonfatal SV encephalitis of immunocompetent BALB/cJ and immunodeficient scid/CB17 mice. IL-1 beta and IL-6 mRNAs were detected in uninfected mice before infection and were up-regulated within 24 h. TGF-beta mRNA was also constitutively expressed in uninfected mice. LIF mRNA was occasionally detected in uninfected mice but increased in amounts only in BALB/cJ not scid mice after infection. TNF-alpha, IL-4, and IL-10 mRNAs were not found in uninfected mice but were induced within 24 h and continued to rise through 7 days after infection with substantially higher levels in BALB/cJ than scid mice. These data suggest that intrinsic brain cells produce IL-1, IL-4, IL-6, IL-10, LIF, and TGF-beta mRNAs in response to viral infection. IFN-gamma and IL-2 mRNAs were detected only in BALB/cJ mice and not until 3 days after infection with the initiation of inflammation. IL-4 and IL-10 mRNAs were more persistent and more easily detectable than IL-2 and IFN-gamma mRNAs. These data suggest a predominant type 2 cytokine response in the brain during SV encephalitis. BALB/cJ mice infected with a neurovirulent strain of SV (NSV), had 100% mortality, whereas NSV-infected scid mice developed persistent nonfatal infection. Inflammation was more intense in NSV-infected mice, however, no substantial differences in cytokine mRNA levels were detected when compared with mice with nonfatal SV infection suggesting that the cytokines measured do not in and of themselves lead to fatal central nervous system disease.
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PMID:Intracerebral cytokine mRNA expression during fatal and nonfatal alphavirus encephalitis suggests a predominant type 2 T cell response. 830 Nov 32

For a series of immunological diseases including asthma, inflammatory arthritis and experimental allergic encephalomyelitis the non-classical major histocompatibility complex (MHC) genetics of man and mouse has been making rapid progress. Information is available not only for the disease associations of individual candidate genes but also from the first genome scans. In both species the proinflammatory cytokine genes and/or their related receptors and inhibitors (IL-1, IL-1r, IL-1ra, IL-2, IL-6r, TNF-alpha), and to a lesser extent the anti-inflammatory cytokine IL-4 are implicated as candidate control elements. In contrast, genes for the signalling and adhesion CD molecules have so far been inconspicuous. Most of the polymorphisms so far detected have been in the regulatory sequences of these genes, rather than in the exons. It is suggested that the benefit conferred on an individual by greater flexibility in its immunoregulatory machinery may be responsible for maintaining this form of polymorphism.
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PMID:Non-classical-MHC genetics of immunological disease in man and mouse. The key role of pro-inflammatory cytokine genes. 889 33

In experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, we showed previously that depletion of gammadelta T cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity. We now report on the effect of gammadelta T cell depletion on expression of five cytokine genes, IL-1, IL-6, TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset, onset, height, and recovery phases of EAE, and on expression of type II nitric oxide synthase. In control animals, the mRNAs for IL-1 and IL-6 rose dramatically at disease onset and peaked before disease height, whereas the mRNAs for TNF, lymphotoxin, and IFN-gamma rose more slowly and peaked with peak of disease. In GL3-treated animals, a dramatic reduction in all five cytokines was noted at disease onset, but only IFN-gamma remained significantly reduced at a time point equivalent to height of disease in control animals. ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point. Studies of type II NOS also demonstrated a significant reduction in both mRNA and protein expression at the height of disease in GL3-treated animals. These results suggest that gammadelta T cells contribute to the pathogenesis of EAE by regulating the influx of inflammatory cells into the spinal cord and by augmenting the proinflammatory cytokine profile of the inflammatory infiltrates.
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PMID:The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis. 963 9


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