Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS). We previously reported upregulation of gene expression for a number of proinflammatory cytokines, interleukin-1beta (IL-1beta), IL-2, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, and interferon-gamma (IFN-gamma), in the CNS of mice with myelin basic protein (MBP)-induced relapsing EAE by using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). However, in these mice there was no significant increase of gene expression for immunoregulatory cytokines (IL-4, IL-10, transforming growth factor-beta [TGF-beta]). We report here that gene expression for both proinflammatory and immunoregulatory cytokines increased during the course of disease in the CNS of mice with myelin oligodendrocyte glycoprotein (MOG)-induced nonrelapsing EAE. These results indicate that the gene expression pattern of immunoregulatory cytokines in the CNS may be different between MBP-induced and MOG-induced EAE and that it may influence the type of disease. Accordingly, the course of the disease may be influenced by the interplay between the proinflammatory and immunoregulatory cytokines.
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PMID:The development of autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein is associated with an upregulation of both proinflammatory and immunoregulatory cytokines in the central nervous system. 966 Feb 49

We previously observed Th1-dominated response in the central nervous system (CNS) of mice during the course of experimental allergic encephalomyelitis (EAE) with a semiquantitative reverse transcriptase-polymerase chain reaction (RT/PCR) analysis. We report here that mRNA levels for both inflammatory cytokines including interleukin (IL)-1beta, IL-2, IL-6, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and TNF-beta and immunoregulatory cytokines including IL-4, IL-10 and transforming growth factor (TGF)-beta were up-regulated in the preclinical and/or acute phase but down-regulated in the recovery phase of EAE in lymph node (LN) of mice. Similar profiles for cytokine mRNA levels were also observed in spleen and peripheral blood mononuclear cells (PBMC). The present study also showed that a significant down-regulation of the mRNA level for IL-6 in the acute phase as compared with the preclinical phase, and a significant reduction of the mRNA level for TGF-beta in the preclinical and acute phase as compared with the corresponding mRNA levels in the control mice treated with complete Freund's adjuvant alone were characteristic in peripheral immune organs of mice with EAE. These results indicate that no particular bias in cytokine production occurred in peripheral immune organs of mice with actively induced relapsing EAE, and that the relative reduction in production of TGF-beta or IL-6 in peripheral circulation might participate in the induction or remission of EAE, respectively. Our results using the animal model of multiple sclerosis (MS) suggested that the mRNA levels for IL-6 and TGF-beta in PBMC from patients with MS may be a good indicator to assess the disease activity or to predict relapse.
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PMID:The pattern of cytokine gene expression in lymphoid organs and peripheral blood mononuclear cells of mice with experimental allergic encephalomyelitis. 967 Aug 56

Experimental autoimmune encephalomyelitis follows a chronic relapsing course in several inbred strains of mice. To address the role of T cells in recovery and relapse, the clinical course of EAE was compared in C57BL/6 (B6) normal and immunodeficient mice following active immunization with MOG p35-55 or adoptive transfer of encephalitogenic peptide-specific T cell lines. The course of actively-induced EAE in B6 wild-type and IL-4 -/- mice was similar. B6 IL-4 -/- mice recovered normally from acute passive EAE, but did not relapse in contrast to wild-type B6 mice. EAE was progressive in B6 RAG -/- and alpha/beta TCR -/- mice, but the disease course could be arrested by infusion of normal spleen cells. When non-activated MOG peptide-specific T cells were transferred to wild-type or alpha/beta TCR -/- mice, spontaneous disease ensued in the mutants only.
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PMID:Acute and relapsing experimental autoimmune encephalomyelitis in IL-4- and alpha/beta T cell-deficient C57BL/6 mice. 967 Aug 59

Inflammatory cells were obtained from the spinal cords of rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the expression of mRNA for interleukin-2 (IL-2), IL-4, IL-10 and interferon-gamma (IFN-gamma) by cells from groups of rats studied 10-21 days after inoculation. On all days of study, the inflammatory cells, which were predominantly lymphocytes, expressed mRNA for IL-2, IL-4, IL-10 and IFN-gamma. In the mRNA from normal rat spinal cord tissue, there was little expression of cytokine mRNA. Cells from a short-term MBP-reactive T cell line expressed all the cytokines. Densitometry was used to measure the products of PCR, to assess the expression of each cytokine relative to that of beta-actin. IL-2 mRNA was expressed throughout the course of disease and reached a peak on day 18, during late clinical recovery. IFN-gamma was expressed throughout the course of the disease and was also high during late recovery. IL-4 mRNA was present in the spinal cord throughout the course of the disease, with a slight rise during late recovery. Relative expression of IL-10 rose to a peak on days 17-19, during late recovery from clinical disease. This study indicates that IL-2, IL-4, IL-10 and IFN-gamma are expressed by inflammatory cells in the spinal cord in EAE, with the relative expression of all cytokines being high during late clinical recovery.
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PMID:Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants. 968 21

Susceptibility to autoimmunity has been associated with polarization of Th1/Th2 balance in immune system towards the Th1-type of reactivity. We report here that orally administered quinoline-3-carboxamide (Linomide) selectively downregulates Th1 response in BALB/c and SJL mice, leading to reduction of autoimmunity in the BALB/c and SJL models of experimental allergic encephalomyelitis (EAE). This was shown by prevention of EAE in Th1 responding SJL mice and partial downregulation of EAE in Th2-prone BALB/c mice. In a BALB/c model of EAE, in which infection with Semliki Forest A7 virus (SFV-A7) is used for enhancement of autoimmunity, clinical signs of EAE were reduced while mortality due to viral infection in the CNS was enhanced. Selective downregulation of the Th1 response by Linomide also rendered initially resistant SJL mice susceptible to SFV-A7 CNS infection. This was shown by immunohistochemical detection of extensive deposits of viral antigen in numerous perivascular foci within the CNS and abolished virus antigen-specific lymphocyte reactivity in Linomide-treated SJL mice. In addition, analysis of spleen cell cytokine mRNA production profile revealed decreased number of IFN-gamma producing cells in both SJL and BALB/c mice, reduced number of IL-12p40 producing cells in SJL and increased number of 12p40 producing cells in BALB/c mice along with slightly increased IL-4 production in both strains of mice. These results indicate that oral treatment with Linomide induces selective downregulation of Th1 reactivity causing reduction of autoimmunity and increased susceptibility to SFV-A7 CNS infection. Selective downregulation of Th1 response is a desired effect in the treatment of autoimmune diseases but our results suggest that the benefits have to be balanced against the possible loss in immunoprotection against pathogens.
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PMID:Selective downregulation of Th1 response by Linomide reduces autoimmunity but increases susceptibility to viral infection in BALB/c and SJL mice. 968 38

We have previously shown that following oral administration of myelin basic protein (MBP), regulatory T cells are generated from gut-associated lymphoid tissue and that these cells suppress experimental allergic encephalomyelitis (EAE). These regulatory T cells produce transforming growth factor-beta (TGF-beta) with various amounts of IL-4 and IL-10 and these TGF-beta-secreting T cells have been termed Th3 cells. T cells in lymphoid organs drained by mucosal sites secrete IL-4 as a primary T cell growth factor. In the present study, we examined the role of IL-4 on oral tolerance and in the generation of TGF-beta secreting cells. Treatment of (PLJ x SJL)F1 mice with intraperitoneal (i. p.) IL-4 and low-dose oral MBP (0.5 mg) given three times reduced the severity of EAE, whereas i.p. injection of IL-4 alone or oral MBP alone given in these suboptimal doses, showed no protection. Spleen cells from protected mice produced increased amounts of TGF-beta and reduced IFN-gamma upon stimulation with MBP in vitro. Mucosal MBP-specific IgA production was significantly increased in IL-4 plus MBP fed animals. Moreover, oral administration of IL-4 (1 microg per feeding) also enhanced the suppression of EAE by oral MBP and this protective effect was reversed by administration of anti-TGF-beta antibody in vivo. Reverse transcription-PCR showed enhanced suppression of IFN-gamma in Peyer's patch in animals fed MBP and IL-4 versus those fed MBP alone. We then investigated the role of IL-4 in the generation of TGF-beta-secreting cells using MBP Ac1-11 TCR transgenic animals. Cells were cultured with IL-2, IL-4, or IFN-gamma in the presence of MBP and limiting dilution analysis for cytokine-secreting cells performed. We found that IL-4, but not IL-2 or IFN-gamma, generated TGF-beta-secreting T cells from naive splenic T cells and that these cells provided help for IgA production. These findings demonstrate that IL-4 is a differentiation factor for TGF-beta-secreting Th3 cells and oral IL-4 has a synergistic effect on low-dose oral tolerance that is associated with increased TGF-beta secretion.
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PMID:IL-4 is a differentiation factor for transforming growth factor-beta secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. 975 65

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) which is often used as an animal model for human multiple sclerosis (MS). The disease is mediated by autoreactive lymphocytes recognizing myelin self-antigens. The autoreactive lymphocytes elicit autoimmune inflammation in the CNS and lead to demyelination and loss of neurological functions. Although autoimmune encephalomyelitis can lead to irreversible nervous tissue injury and demise of animals, EAE is often characterized by spontaneous disease recovery or remission. It is not known how EAE progression is regulated, nor is it clear how autoimmune inflammation in the CNS can resolve while the myelin-specific lymphocytes and myelin self-antigens remain in the animals. Cytokines, especially TH2-type cytokines, have long been suggested to play a role in regulating EAE. However, experiments using recombinant cytokines or neutralizing antibodies to cytokines have generated conflicting results. To determine the roles of interleukin (IL)-4 and IL-10 in experimental autoimmune encephalomyelitis, we have studied mice deficient in IL-4 or IL-10. We found that IL-10- but not IL-4-deficient mice had accelerated EAE following immunization with myelin oligodendrocyte glycoprotein (MOG). Importantly, spontaneous recovery from EAE occurred in normal and IL-4-deficient mice, but not in mice deficient in IL-10. Furthermore, we established that the acceleration of EAE in IL-10-deficient mice was associated with a decrease in IL-4 and an increase in IFN-gamma production in response to MOG antigen. These results strongly suggest that IL-10 plays a crucial role in the progression and recovery of autoimmune encephalomyelitis.
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PMID:Acceleration of experimental autoimmune encephalomyelitis in interleukin-10-deficient mice: roles of interleukin-10 in disease progression and recovery. 975 42

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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