UMLS:C0014070 - FACTA Search

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Query: UMLS:C0014070 (encephalomyelitis)
13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of IL-6 in experimental autoimmune encephalomyelitis (EAE) provoked by myelin oligodendrocyte glycoprotein (MOG) was investigated using IL-6-deficient mice. We show here that IL-6-deficient mice were resistant to the MOG-induced EAE as compared to wild-type mice (one out of 18 versus 17 out of 20). The delayed-type hypersensitivity response, lymphocyte proliferation response and antibody reactivity to MOG in IL-6-deficient mice were significantly lower than those in wild-type mice. Furthermore, the histological examination revealed that no infiltration of inflammatory cells was observed in the central nervous system of IL-6-deficient mice. These results indicate that IL-6 may play a crucial role in the induction phase of EAE. Given the potential relevance of this animal model for multiple sclerosis (MS), it is possible that anti-IL-6 therapy may be useful in the prevention of relapses of MS.
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PMID:IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. 964 18

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 (EAE) is induced by immunization with myelin components including myelin oligodendrocyte glycoprotein (MOG). Myelin-specific Th1 cells enter the central nervous system (CNS) via binding of very late antigen 4 (VLA-4) to the endothelial vascular cell adhesion molecule 1 (VCAM-1). In the present study, mice with a homologous disruption of the gene encoding IL-6 are found to be resistant to MOG-induced EAE as evidenced by absence of clinical symptoms, minimal infiltration of CD3+ T cells and monocytes into the CNS and lack of demyelination. The failure to induce EAE in IL-6-/- mice is not due to the absence of priming, since lymphocytes of immunized IL-6-/- mice proliferate in response to MOG and produce pro-inflammatory cytokines including IL-2 and IFN-gamma. However, in MOG-immunized IL-6-/- mice, serum anti-MOG antibody titers were found to be drastically reduced. This observation is unlikely to be responsible for resistance to EAE, because B cell-deficient (microMT) mice proved to be fully susceptible to the disease. A striking difference between MOG-immunized wild-type (wt) and IL-6-/- mice was the expression of endothelial VCAM-1 and ICAM-1, which were dramatically up-regulated in the CNS in wt but not in IL-6-/- mice. Taking into account recent studies on the role of VCAM-1 in the entry of Th1 cells into the CNS, the absence of VCAM-1 on endothelial cells in IL-6-/- mice may explain their resistance to EAE.
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PMID:IL-6-deficient mice resist myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis. 969 87

In the present study, we examined the therapeutic effects of T-614 (3-formylamino-7-methylsulfonylaminoxy-4H-1-benzopyran-4-one), a new anti-rheumatic drug, on a T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis (EAE). T-614 dose-dependently suppressed the development of active EAE induced in Lewis rats by immunization with myelin basic protein (MBP) when administered for 2 weeks starting on the day of immunization (day 0 to 14). Amelioration of clinical signs was also obtained by the treatment at the effector phase (day 7 to 14) of the disease. Furthermore, T-614 treatment of recipient rats that had received MBP-sensitized lymphoid cells resulted in suppression of the clinical severity of EAE. Immunohistological examination revealed that the number of TCR alpha beta-expressing T cells and the extent of MHC class II expression in the spinal cord of rats treated with T-614 was markedly reduced. In vitro study using MBP-specific T cells showed that the addition of T-614 inhibited the proliferative responses of T cells and the production of pro-inflammatory cytokines such as IFN-gamma, IL-6 and TNF produced by T and accessory cells. Taken together, these findings imply that T-614 suppresses the development of EAE by inhibiting the proliferation of autoreactive T cells and pro-inflammatory cytokine production not only by T cells but also by macrophages/microglia. This may be attributable to the result that T-614 is more effective at the effector phase rather than the induction phase. Thus, this drug has a potential value for the treatment of various T cell-mediated autoimmune diseases including multiple sclerosis (MS) as well as rheumatoid arthritis.
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PMID:A new anti-rheumatic drug, T-614, effectively suppresses the development of autoimmune encephalomyelitis. 972 23

Theiler's murine encephalomyelitis virus (TMEV) infection of a susceptible strain of mice results in virus persistence in the brain and chronic primary immune-mediated demyelination, which resembles multiple sclerosis. Recent attention has focused on the anti-inflammatory and immunosuppressive properties of interleukin-6, a pleiotropic cytokine involved in the regulation of immunological responses, acute phase protein production and hematopoiesis. Anandamide (arachidonoyl ethanolamine) is a natural brain constituent that binds a specific brain cannabinoid receptor. In this study we investigated whether anandamide can modify interleukin-6 production by primary cultures of murine brain cortical astrocytes infected with TMEV. Astrocytes from susceptible (SJL/J) and resistant (BALB/c) strains of mice infected with TMEV (10(5)PFU/well) increased IL-6 release over a period of 24 h. Anandamide caused an enhancement of the release of IL-6 by TMEV-infected astrocytes in a concentration-dependent manner (1-25 microM). Treatment of TMEV-infected astrocytes with 10 microM arachidonyl trifluoromethyl ketone, a potent inhibitor of the amidase that degrades anandamide, was found to potentiate the effects of anandamide on IL-6 release. A novel and selective cannabinoid receptor antagonist, SR 141617A, blocked the enhancing effects of anandamide on IL-6 release by TMEV-infected astrocytes, suggesting a cannabinoid receptor-mediated pathway. The physiological implications of these results are unknown, but may be related to the hypothesis of the protective effects of cannabinoids on neurological disorders like multiple sclerosis.
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PMID:The endogenous cannabinoid anandamide potentiates interleukin-6 production by astrocytes infected with Theiler's murine encephalomyelitis virus by a receptor-mediated pathway. 973 48

Although autoreactive T cells recognizing self myelin Ags are present in most individuals, autoimmune disease of the central nervous system is a relatively rare medical condition. Development of autoimmune disease may require not only the presence of autoreactive T cells but also that autoreactive T cells become activated. Activation of T cells may require a minimum of two signals: an Ag-specific signal delivered by MHC-peptide complex and a second signal delivered by costimulatory molecules or cytokines. Although in vitro studies have suggested that cytokines, especially proinflammatory cytokines such as IL-1, IL-6, and TNF are involved in T cell activation, their precise roles in vivo are not clear. To determine the roles of proinflammatory cytokines in T cell activation in vivo and in the development of autoimmune disease, we have studied experimental autoimmune encephalomyelitis (EAE) in mice deficient in IL-6. We found that IL-6-deficient mice were completely resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG), whereas IL-6-competent control mice developed EAE characterized by focal inflammation and demyelination in the central nervous system and deficiency in neurologic functions. Furthermore, we established that the resistance to EAE in IL-6-deficient mice was associated with a deficiency of MOG-specific T cells to differentiate into either Th1 or Th2 type effector cells in vivo. These results strongly suggest that IL-6 plays a crucial role in the activation and differentiation of autoreactive T cells in vivo and that blocking IL-6 function can be an effective means to prevent EAE.
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PMID:IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: roles of IL-6 in the activation and differentiation of autoreactive T cells. 986 71

CD45 is involved in the regulation of lymphocyte activation, and it has been demonstrated that ligation of CD45 induces apoptosis of T and B lymphocytes. Recently anti-CD45RB antibody therapy was shown to block acute allograft rejection in a mouse model of transplantation. Therefore, we wanted to examine the effects of anti-CD45RB antibody treatment on the course of an autoimmune disorder, experimental allergic encephalomyelitis (EAE), a Th1-mediated process. Mice immunized with myelin basic protein and treated with anti-CD45RB antibody did not develop EAE. Histologically, there was no evidence of lymphocytic infiltrates in the central nervous system. T cell proliferation and TNF-alpha production were significantly decreased in anti-CD45RB-treated mice. Furthermore, there was a significant reduction in the production of other Th1 cytokines including interferon-gamma and IL-2, but not IL-4 or IL-6. However, levels of a number of adhesion markers or markers of activation such as VLA-4 and LFA-1 on T cells were no different in treated versus control animals. Thus, anti-CD45RB can prevent EAE and appears to do so by altering T cell proliferation and cytokine production.
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PMID:Prevention of experimental allergic encephalomyelitis by an antibody to CD45RB. 987 18

SJL mice are susceptible to inflammatory autoimmune diseases of the central nervous system (CNS), while BALB/c mice are relatively resistant. To understand differences in immune responses that may contribute to autoimmune neurologic disease, we compared the responses of SJL and BALB/c mice to infection with Sindbis virus, a virus that causes acute nonfatal encephalomyelitis in both strains of mice. Clearance of virus was similar, but SJL mice developed a more intense inflammatory response in the brain and spinal cord and inflammation persisted for several weeks. Analysis of lymphocytes isolated from brains early after infection showed an absence of NK cells in SJL mice, while both strains of mice showed CD4+ and CD8+ T cells. During the second week after infection, CD4+ T cells increased in SJL mice and the proportion of CD8+ T cells decreased, while the opposite pattern was seen in BALB/c mice. Expression of IL-10 mRNA was higher and IL-4 mRNA was lower in the brains of infected SJL than in BALB/c mice, while expression of the mRNAs of IL-6, IL-1beta, TNFalpha, and the Th1 cytokines IL-2, IL-12, and IFN-gamma was similar. Lymphocytes isolated from the CNS of SJL mice produced large amounts of IL-10. CNS lymphocytes from both strains of mice produced IFN-gamma in response to stimulation with Sindbis virus, but not in response to myelin basic protein. These data suggest that IL-10-producing CD4+ T cells are differentially recruited to or regulated within the CNS of SJL mice compared with BALB/c mice infected with Sindbis virus, a characteristic that may be related to low levels of IL-4, and is likely to be involved in susceptibility of SJL mice to CNS inflammatory diseases.
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PMID:The inflammatory response to nonfatal Sindbis virus infection of the nervous system is more severe in SJL than in BALB/c mice and is associated with low levels of IL-4 mRNA and high levels of IL-10-producing CD4+ T cells. 997 22

Chemokines may be important in the control of leukocytosis in inflammatory disorders of the central nervous system. We studied cerebral chemokine expression during the evolution of diverse neuroinflammatory disorders in transgenic mice with astrocyte glial fibrillary acidic protein-targeted expression of the cytokines IL-3, IL-6, or IFN-alpha and in mice with experimental autoimmune encephalomyelitis. Distinct chemokine gene expression patterns were observed in the different central nervous system inflammatory models that may determine the phenotype and perhaps the functions of the leukocytes that traffic into the brain. Notably, high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis. In both these neuroinflammatory models, C10 RNA and protein expressing cells were predominantly macrophage/microglia and foamy macrophages present within demyelinating lesions as well as in perivascular infiltrates and meninges. Intracerebroventricular injection of recombinant C10 protein promoted the recruitment of large numbers of Mac-1(+) cells and, to a much lesser extent, CD4(+) lymphocytes into the meninges, choroid plexus, ventricles, and parenchyma of the brain. Thus, C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show, also acts as a potent chemotactic factor for the migration of these leukocytes to the brain.
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PMID:C10 is a novel chemokine expressed in experimental inflammatory demyelinating disorders that promotes recruitment of macrophages to the central nervous system. 1023 56

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