Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-10 is an immunoregulatory cytokine that can modulate immune processes, inhibiting the expression of inflammatory T(h)1 type responses as well as affecting antigen-presenting cell function. In addition, IL-10 has been shown to be active at mucosal surfaces. In the present study, we examined the role of IL-10 on orally and nasally induced tolerance. Treatment of (PL/J x SJL)F(1) mice with low-dose oral myelin basic protein (MBP) (0.5 mg) and simultaneous oral IL-10 given 3 times reduced the severity and incidence of experimental autoimmune encephalomyelitis (EAE), whereas administration of oral IL-10 alone or MBP alone given in these doses had no effect. Lymphocytes from mice treated orally with MBP and IL-10 proliferated less, and produced decreased amounts of IFN-gamma and IL-2 and increased amounts of IL-10 and transforming growth factor-beta upon in vitro stimulation with MBP. Nasal administration of antigen and IL-10 reduced proliferative responses and IFN-gamma production, increased IL-10 production, and enhanced protection from EAE. In addition, oral IL-10 combined with oral myelin oligodendrocyte glycoprotein (MOG) 35-55 reduced relapses in MOG-induced EAE in the NOD mouse, as well as enhanced the protective effect of oral insulin in the NOD model of diabetes. These results demonstrate that IL-10 is biologically active at mucosal surfaces and can act synergistically to enhance the tolerogenic effects of mucosally administered antigen.
 ...
PMID:Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes. 1136 11

Stiff man syndrome (SMS), an uncommon neurological disease, is characterised by symmetrical muscle stiffness and spasms that often lead to skeletal deformity. Variants of the syndrome may involve one limb only (stiff leg syndrome), a variety of additional neurological symptoms and signs such as eye movement disturbances, ataxia, or Babinski signs (progressive encephalomyelitis with rigidity and myoclonus), or be associated with malignant disease (paraneoplastic SMS). Antineuronal autoimmunity and accompanying autoimmune diseases, most often insulin-dependent diabetes mellitus, are characteristic features of SMS and its variants. The condition is frequently misinterpreted as psychogenic movement disturbance, but electromyographic abnormalities and the presence of autoantibodies against glutamic acid decarboxylase (GAD) in both serum and cerebrospinal fluid help to establish the correct diagnosis. The aetiology of SMS is obscure. However, several features suggest that SMS is an autoimmune-mediated chronic encephalomyelitis. In line with this hypothesis, immunomodulation with a front-loaded methylprednisolone regimen reduces stiffness and spasms and improves other neurological symptoms in the majority of patients. Plasmapheresis or intravenous immunoglobulins are effective less frequently. For symptomatic treatment, the benzodiazepines are drugs of first choice. An alternative of last resort is baclofen administered intrathecally via an implanted pump device.
 ...
PMID:Stiff man syndrome. 1151 Jun 22

The ability of superantigens to activate large numbers of T cells suggests that they may play a role in the course of autoimmune disorders. Data from several animal models of autoimmune disorders including experimental allergic encephalomyelitis and collagen induced arthritis supports this hypothesis. Administration of bacterial superantigens can induce an exacerbation of the autoimmune process in these models, or induce disease de novo in the appropriately immunized animal. Studies of several human disorders including rheumatoid arthritis, Kawasaki disease, insulin-dependent diabetes, and psoriasis lend credence to the concept that bacterial superantigens may play a role in the pathogenesis of these diseases. Nevertheless, in some cases, depending on the timing of administration and the model, superantigens may lead to an amelioration of the autoimmune process. Based on these results in seems logical to conclude that superantigens can have a significant impact on the course of the immune and autoimmune mediated disorders.
 ...
PMID:Superantigens and their role in autoimmune disorders. 1172 24

Based on the tolerogenic properties of IgG carriers and B cell Ag presentation, we developed a retrovirally mediated gene expression approach for treatment of autoimmune conditions. In this study, we show that the IgG-Ag retroviral constructs, expressing myelin basic protein (MBP) or glutamic acid decarboxylase in B cells, can be used for the treatment of murine models for multiple sclerosis and diabetes. Transduction of syngeneic B cells with MBP-IgG leads to the amelioration of ongoing experimental allergic encephalomyelitis induced by the transfer of primed cells from PLxSJL F(1) mice with ongoing disease and could be effective even after symptoms appeared. This effect is specific and does not involve bystander suppression because treatment with MBP-IgG does not affect disease induced after immunization with proteolipid protein immunodominant peptide plus MBP. Interestingly, if donor B cells are derived from gld mice (Fas ligand-negative), then tolerance is not induced with a model Ag although there was no evidence for Fas ligand-mediated deletion of target T cells. In spontaneous diabetes in nonobese diabetic mice, we were able to stop the ongoing autoimmune process by treatment at 7-10 wk with glutamic acid decarboxylase-IgG retrovirally transduced B cells, or attenuate it with B cells transduced with an insulin B chain (B9-23) epitope IgG fusion protein. Furthermore, IgG fusion protein gene therapy can also protect primed recipients from Ag-induced anaphylactic shock, and thus does not cause immune deviation. These results demonstrate proof of principle for future efforts to develop this approach in a clinical setting.
 ...
PMID:Gene transfer of Ig-fusion proteins into B cells prevents and treats autoimmune diseases. 1197 Oct 30

Naive non-obese diabetic (NOD/LtJ) mice spontaneously produce natural IgG autoantibodies against self-antigens associated with the experimental autoimmune diseases to which they are susceptible: insulin-dependant diabetes mellitus, systemic lupus erythematosus and experimental autoimmune encephalomyelitis. We discovered recently that NOD/LtJ mice also spontaneously produce IgG antibodies to the acetylcholine receptor (AchR), an antigen that can induce experimental autoimmune myasthenia gravis (EAMG) in susceptible rodents. However, there are no reports indicating that NOD/LtJ mice are susceptible to EAMG. To test whether the presence of spontaneous IgG autoantibodies can predict susceptibility to an autoimmune disease, we challenged NOD/LtJ mice using a standard protocol to induce EAMG. We now report that NOD/LtJ mice developed EAMG, although to a somewhat lesser degree than did C57BL/6 mice, a strain regarded as highly susceptible to the disease. Both strains produced comparable levels of immune antibodies to AchR of the complement-fixing isotypes IgG2a and IgG2b; however, NOD/LtJ mice produced significantly more IgG1. An antigen-specific T cell proliferative response to AchR of the same magnitude was detected in both strains, together with the secretion of similar amounts of IFN-gamma. Thus, NOD/LtJ mice are susceptible to EAMG and disease induction is accompanied by immune responses comparable to those seen in the susceptible strain C57BL/6. These results support the association between specific, natural IgG autoantibodies and susceptibility to the induction of a particular autoimmune disease.
 ...
PMID:Experimental autoimmune myasthenia gravis in naive non-obese diabetic (NOD/LtJ) mice: susceptibility associated with natural IgG antibodies to the acetylcholine receptor. 1250 21

Autoimmune diseases frequently develop as a result of an abnormal activation of autoreactive T cells, excessive production of proinflammatory cytokines, particularly by CD4(+) Th1 cells, and subsequent tissue destruction. Cytokine-dependent immunotherapy can be applied to alter the balance between Th1 and Th2 cell activity, or proinflammatory versus immunosuppressive cytokine profiles. Cytotoxic T lymphocyte (CTL) and/or macrophage activity can also be suppressed. Gene transfer offers numerous advantages for the in vivo delivery of cytokines or their receptors for immunotherapeutic use. We have relied on the injection of naked plasmid DNA into skeletal muscle to deliver therapeutic genes. In particular, we have successfully used this approach to deliver neutralizing cytokine receptors such as interferon gamma (IFNgamma)-receptor-Ig fusion proteins or anti-inflammatory cytokines such as transforming growth factor beta-1 (TGF-beta1) and interleukin 4 (IL-4). Intramuscular gene therapy is effective in protecting against several experimental autoimmune diseases including insulin-dependent diabetes mellitus (IDDM), experimental allergic encephalomyelitis (EAE), and systemic lupus erythematosus (SLE). Another promising approach involves DNA vaccination by plasmid-based codelivery of genes encoding an autoantigen and either a cytokine or other immunomodulatory molecule. Plasmid vectors offer interesting advantages over viral vectors, since they are simple to produce, non-immunogenic and non-pathogenic. They can be repeatedly administered with relatively prolonged periods of expression in vivo, ranging from weeks to months after each injection. Plasmid-based intramuscular gene transfer has great therapeutic potential in the areas of autoimmune and inflammatory disorders.
 ...
PMID:Immune modulation by plasmid DNA-mediated cytokine gene transfer. 1257 Jun 78

Encephalomyocarditis (EMC) virus induces insulin-dependent diabetes and myocarditis in several strains of mice. The T-cell receptor (TCR) Vbeta genes of infiltrating T cells in the pancreas and myocardium of BALB/C mice infected with EMC virus D-variant (EMC-D virus) were analyzed. Using a nested two-step polymerase chain reaction (PCR), TCR Vbeta cDNAs were cloned and sequenced. Two and four kinds of TCR Vbeta clones were obtained from T cells infiltrating into the pancreas and myocardium of BALB/C mice infected with EMC-D virus, respectively. The infiltrating lymphocytes in the diabetic mice expressed Vbeta 8.1, 8.2, and 8.3 genes predominantly. Previously, the use of Vbeta 8.2 has been reported in autoimmune diseases such as murine experimental allergic encephalomyelitis (EAE) and non-obese diabetic (NOD) mouse. This study suggests that mice infected with EMC virus are a useful animal model for autoimmune diseases such as insulin-dependent diabetes.
 ...
PMID:Analysis of T-cell receptor Vbeta gene from infiltrating T cells in insulitis and myocarditis in encephalomyocarditis virus-infected BALB/C mice. 1455 Feb 73

The skin is both an essential barrier for host defense and an important organ of immunity. In this study, we show that the application of cholera toxin to intact mouse skin induces and enhances autoimmune diseases affecting organs at distant anatomic sites, whereas its administration by the mucosal route has been reported to have the opposite effect. First, the CNS autoantigen myelin oligodendrocyte glycoprotein 35-55, when applied repeatedly with cholera toxin to the intact skin of healthy C57BL/6 mice, induced relapsing paralysis with demyelinating immunopathologic features similar to multiple sclerosis. Second, the application of cholera toxin in the absence of autoantigen exacerbated the severity of conventional experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein in CFA. Third, the application of cholera toxin to the intact skin of NOD/Lt mice, with or without insulin B peptide 9-23, exacerbated insulitis and T lymphocyte-derived IFN-gamma and IL-4 production in the islets of Langerhans, resulting in an increased incidence and rate of onset of autoimmune diabetes. The data presented in this study highlight the different outcomes of adjuvant administration by different routes. Because dermal application of cholera toxin, and other bacterial products with similar adjuvant activities, is being developed as a clinical vaccination strategy, these data raise the possibility that it could precipitate autoimmune disease in genetically susceptible humans.
 ...
PMID:Dermal enhancement: bacterial products on intact skin induce and augment organ-specific autoimmune disease. 1468 38

Insulin-like growth factor 1 increases both the number of oligodendrocytes and the amount of axonal myelin produced. The aim of this study was to see whether insulin-like growth factor 1 played a role in white-matter diseases of children. We studied insulin-like growth factor 1 in the cerebrospinal fluid of children with various white-matter diseases: (1) children with acute demyelinating events: acute disseminated encephalomyelitis (n = 5), acute transverse myelitis in multiple sclerosis (n = 1), and infarct of the medial cerebral artery causing secondary white-matter changes (n = 1), and (2) children with chronic diseases: delayed myelination (n = 3) and progressive leukodystrophies (n = 4). Insulin-like growth factor 1 was determined by radioimmunoassay with commercially available kits (Mediagnost, Tubingen, Germany). We found markedly lower concentrations of cerebrospinal fluid insulin-like growth factor 1 in the patients than in the 28 age-matched control children (P < .0005). Low cerebrospinal fluid insulin-like growth factor 1 can play a role in the pathology of both acute and chronic white-matter diseases of children.
 ...
PMID:Cerebrospinal fluid insulin-like growth factor 1 is low in acute and chronic white-matter diseases of children. 1583 5

Insulin-like growth factor 1 (IGF-1) has been identified as a critical molecule in the induction of myelination in the central nervous system (CNS). Systemic injection of IGF-1 has been shown to have a varied and transiently protective effect on the clinical course of experimental autoimmune encephalomyelitis (EAE). Since systemic IGF-1 can also modulate peripheral immune lymphocytes, we examined whether a sustained and local delivery of IGF-1 into the spinal cord would have any influence on the chronic course of EAE in C57/BL6 mice. The capability of adeno-associated virus (AAV) to be retrogradely transported efficiently from muscle to motor neurons of the spinal cord was used to overcome the difficulty routinely encountered when attempting chronic delivery of molecules into the CNS. We demonstrate that AAV-mediated delivery of IGF-1 in CNS did not have any beneficial effect on the clinical course of EAE. Injection of AAV-IGF1 after induction of the disease worsened the clinical symptoms. Furthermore, CNS expression of IGF-1 did not affect the pathogenic anti-MOG T cell response, as examined by proliferation and cytokine secretion. Thus, enhanced expression of IGF-1 in the CNS during inflammation does not have a significant effect on myelination. These data have important implications for the potential use of IGF-1 in the treatment of multiple sclerosis.
 ...
PMID:Targeted expression of IGF-1 in the central nervous system fails to protect mice from experimental autoimmune encephalomyelitis. 1612 Apr 66


<< Previous 1 2 3 4 5 6 Next >>