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)

Since Morton and Siegel's epochal experiments 30 years ago animal models have been successfully utilized both for transfer and resolution of autoimmune diseases (AID). More recently human lymphocyte xenografts have reproduced clinical AID in SCID mice. Allogeneic stem cell transplantation demonstrated therapeutic potential in fully developed autoimmune disease. Mixed allogeneic chimerism induced by a sublethal approach has also been shown to prevent and even reverse autoimmune insulitis in nonobese diabetic (NOD) mice. More unexpectedly it was found that experimental adjuvant arthritis (AA) and experimental allergic encephalomyelitis (EAE) could be cured by means of total body irradiation (TBI) followed by autologous hemolymphopoietic stem cell (HSC) transplantation. It was postulated that the newly developing T cells might be tolerant to self antigens. The transfer of AID from affected donors to recipients of allogeneic HSC transplants has been reported for many organ-specific AID, including diabetes (IDDM), thyroiditis, myasthenia gravis and thrombocytopenic purpura (AITP); rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) were not transferred. Conversely patients with the combination of AID and a severe blood disease (leukemia, aplasia) were cured of both diseases following allogeneic BMT, with the notable exception of a relapse in a patient with RA despite full donor engraftment. Allogeneic transplants are certainly more promising as far as concerns a resolution of AID, because they may also exert a graft-versus-autoimmunity effect by gradually eradicating the recipient's lymphopoiesis, but transplant related mortality (TRM) is considered still too high to employ this procedure consistently. New non-myeloablative conditioning regimens, designed to allow the donor's immune system to take over, are already utilized for malignant and non-malignant hematologic diseases, and may become an attractive option for severe, refractory AID. For the time being, however, autologous procedures are still safer, and are being utilized in many projects worldwide. The EBMT/EULAR Registry has collected over 70 patient reports. The more numerous and favorable results have been obtained up to now in multiple scleosis and in systemic lupus erythematosus; the worst in refractory autoimmune thrombocytopenic purpura. No definite conclusions as to the efficacy of autologous HSC transplantation, from marrow or from blood, with or without T-cell depletion, may be drawn at this time, but the feeling is that real cures will be very difficult to obtain by this approach, and that corticosteroid-free remissions and a general lowering of the autoimmune potential will be more realistic goals. Accurate comparisons with already existing aggressive immunosuppressive protocols will become necessary, if possible by means of prospective randomized clinical studies.
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PMID:Stem cell transplantation for severe autoimmune diseases: progress and problems. 979 58

A 28-year-old woman with systemic lupus erythematosus (SLE) suffered recent onset fever, headache, encephalopathy followed by severe, repeated generalized seizures. Investigations revealed limbic encephalitis. Tests for Herpes simplex encephalitis and paraneoplastic encephalomyelitis were negative. High titers anti-ribosomal-P antibodies in the cerebrospinal fluid (CSF) suggested an association with nervous system lupus. No brain biopsy was performed. Treatment was with anti-seizure, anti-viral, and immunomodulating medication.
Lupus 1998
PMID:Nervous system lupus mimics limbic encephalitis. 986

Several investigators have reported the possibility of gene therapy for experimental autoimmune diseases such as type-1 insulin-dependent diabetes (IDDM), experimental allergic encephalomyelitis (EAE), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Although there are no reports about gene therapies for human autoimmune rheumatic diseases including RA and SLE, we reviewed these experimental therapies for model animals and discussed the possibility of gene therapy for human autoimmune rheumatic disorders as a new therapeutic strategy.
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PMID:[Gene therapy in autoimmune rheumatic diseases]. 1007 22

The bm12 mutation in the class II I-A(b)molecule can profoundly influence experimental autoimmune disease, enhancing the development of systemic lupus erythematosus-like syndromes in NZB.H-2(bm12)mice or, conversely, abolishing the susceptibility of C57BL/6J (H-2(b)) mice to the induction of experimental autoimmune myasthenia gravis. We have studied the effect of this mutation on experimental autoimmune encephalomyelitis (EAE), induced in H-2(b)mice by myelin oligodendrocyte glycoprotein (MOG), and recently showed that MOG 35-55 peptide (pMOG 35-55), which represents the immunodominant encephalitogenic region for H-2(b)mice, is also a strong encephalitogen for H-2(bm12)mice. Nevertheless, although the differences in fine epitope specificity and TCR-Vbeta gene usage between encephalitogenic pMOG 35-55-specific T cells from H-2(b)and H-2(bm12)mice were subtle, H-2(bm12)and H-2(b)antigen presenting cells failed to effectively cross-present pMOG 35-55 non-syngeneically to I-A(b)/pMOG 33-55- and I-A(bm12)/pMOG 35-55-specific T cells, respectively. In the present study, we show that the abrogation of the response to pMOG 35-55 by the Th1 encephalitogenic pMOG 35-55-specific T cells upon non-syngeneic cross-presentation is neither due to a cytokine shift to a Th2 pattern, nor a result of anergy induction. Therefore, we suggest that presentation of pMOG 35-55 to I-A(b)/pMOG 35-55-specific T cells via the bm12 class II MHC molecule resulted in ineffective stimulation, similar to a weak agonistic effect.
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PMID:Effect of the bm12 class II mutation on proliferative and cytokine responses of encephalitogenic T cells in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis. 1044 Nov 62

In the past few years, considerable evidence has accumulated to suggest the existence of functionally polarized responses by the CD4+ T helper (Th)--and the CD8+ T cytotoxic (Tc)-cell subsets that depend on the cytokines they produce. The Th1 and Th2 cellular immune response provide a useful model for explaining not only the different types of protection, but also the pathogenic mechanisms of several immunopathological disorders. The factors responsible for the polarization of specific immune response into a predominant Th1 or Th2 profile have been extensively investigated in mice and humans. Evidence has accumulated from animal models to suggest that Th1-type lymphokines are involved in the genesis of organ-specific autoimmune diseases, such as experimental autoimmune uveitis, experimental allergic encephalomyelitis, or insulin-dependent diabetes mellitus. Accordingly, data so far available in human diseases favor a prevalent Th1 lymphokine profile in target organs of patients with organ-specific autoimmunity. By contrast, Th2-cell predominance was found in the skin of patients with chronic graft-versus host disease, progressive systemic sclerosis, systemic lupus erythematosus, and allergic diseases. The Th1/Th2 concept suggests that modulation of relative contribution of Th1- or Th2-type cytokines regulate the balance between protection and immunopathology, as well as the development and/or the severity of some immunologic disorders. In this review, we have discussed the paradigm of Th1 and Th2 cytokines in relation to autoimmunity and allergy.
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PMID:The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. 1058 Jun 39

Prolactin receptors were identified on the membranes of lymphocytes have been demonstrated to secrete prolactin. The decrease, as well as the increase of the prolactin level in the plasma are responsible for immune disorders. Prolactin dysfunction has been described in some autoimmune diseases, such as systemic lupus erythematosus, immune arthritis, uveitis, experimental allergic encephalomyelitis and thyroid disease. The normal prolactin secretion is trophic for the lymphocytes, while the high and also the low levels of prolactin may play an immunosuppressive role.
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PMID:Prolactin secretion and the immune system. 1075 71

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
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PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31

Acute transverse myelitis (ATM) with moderate symptomatology and smaller multiple magnetic resonance imaging lesions is often caused by multiple sclerosis. Severe ATM with extensive magnetic resonance imaging lesions with or without associated meningitis often has a viral cause, particularly in the younger age groups, whereas vascular disorders may prevail among older patients. Previously, one had to rely on indirect evidence such as viral serology or viral identification in throat washings to confirm a diagnosis of myelitis. Thus, mycoplasma myelitis may occur coincident with a mycoplasma pneumonia. Viral myelitis is now often diagnosed by specific polymerase chain reaction of the cerebrospinal fluid, for echovirus, Coxsackie virus, mumps virus, herpes simplex virus or varicella-zoster virus, but an autoimmune component may still be important. An anterior horn syndrome may be produced by the tick-borne encephalomyelitis virus. Severe ATM may also be a postinfectious or postvaccinal disorder [i.e. a partial acute disseminated encephalomyelitis (ADEM)]. Neuromyelitis optica, a combination of severe myelitis and optic neuritis, is often a manifestation of ADEM or systemic lupus erythematosus. Many of these disorders are potentially treatable with specific antiviral agents or immunosuppression. 'Idiopathic' ATM is probably a consequence of inadequate examination and follow up. The differential diagnoses-viral myelitis, multiple sclerosis, ADEM, neuromyelitis optica, spinal arteriovenous malformation and arteritis-should be considered and are usually identified by a rapid diagnostic work-up, leaving few ATM cases undiagnosed.
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PMID:Myelitis. 1087 Dec 57

Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or their inhibitors. After gene transfer, these mediators are produced at relatively constant, non-toxic levels and sometimes in a tissue-specific manner, obviating limitations of protein administration. Therapy with viral or nonviral vectors is effective in several animal models of autoimmunity including Type 1 diabetes mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes encoding transforming growth factor beta, interleukin-4 (IL-4) and IL-10 are most frequently protective. Autoimmune/ inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL-1, IL-12, tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma). Vectors encoding inhibitors of these cytokines, such as IL-1 receptor antagonist, soluble IL-1 receptors, IL-12p40, soluble TNFalpha receptors or IFNgamma-receptor/IgG-Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. We use intramuscular injection of naked plasmid DNA for cytokine or anticytokine therapy. Muscle tissue is accessible, expression is usually more persistent than elsewhere, transfection efficiency can be increased by low-voltage in vivo electroporation, vector administration is simple and the method is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated administration, and are suitable for the treatment of chronic immunological diseases.
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PMID:Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors. 1095 13

There is evidence that an immunoregulatory circuit integrated by immune-derived cytokines and the hypothalamus-pituitary-adrenal (HPA) axis operates during certain pathological conditions. For example, it has been shown that IL-1 is the main mediator of the increase in ACTH and corticosterone blood levels detected in models of viral infection and bacterial endotoxins. This endocrine response has protective effects during septic shock. In experimental models of tumors, there are also clear indications that the increase in glucocorticoid levels detected during the growth of a lymphoma is mediated by immune-derived products and contributes to the inhibition of the inflammatory response. The disruption of the cytokine-HPA axis circuit can predispose to autoimmunity. This has been shown in animal models of spontaneous autoimmune thyroiditis, lupus-like disease, and experimental arthritis. More recently, it has been shown that the proper operation of this circuit contributes to preventing or moderating autoimmunity. The recovery of animals from experimental autoimmune encephalomyelitis (EAE) is clearly dependent on an increase in endogenous glucocorticoid levels. It has been recently shown that this endocrine response is, at least in part, triggered by the immune response to the encephalitogenic antigen and mediated by the endogenous IL-1 produced during the disease. These examples support the concept that the cytokine-HPA circuit plays a protective role during certain pathologies and that its disruption can lead to predisposition to or aggravation of autoimmune diseases.
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PMID:The cytokine-HPA axis circuit contributes to prevent or moderate autoimmune processes. 1115 1


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