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)

The neuropathology has been described of chronic, relapsing experimental allergic encephalomyelitis produced in SJL/J mice given two injections of isogeneic spinal cord in complete Freund's adjuvant, 1 week apart. The inducing inoculum contained no Bordetella pertussis. The central nervous system changes included hemorrhagic lesions and significant nerve fiber depletion during the early stages of disease, demyelination followed by remyelination, influxes of polymorphonuclear leukocytes and hemorrhage with each acute episode, extensive gliosis, and some Schwann cell invasion and myelination within the central nervous system. Since the mouse is a highly accessible species that is immunologically well understood, this model might lend itself to fuller dissection of autoimmune events associated with recurrent demyelination, problems of considerable significance to multiple sclerosis research.
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PMID:Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. 706 21

Ten inbred strains of mice were tested for their susceptibility to experimental allergic encephalomyelitis (EAE) after sensitization with mouse spinal cord in complete Freund's adjuvant followed by booster injections of Bordetella pertussis. The results extended previous findings in that not all susceptible mice possessed the H-2s haplotype, but mice with an H-2q background (DBA1/J strain) were also susceptible. Neuropathologic examination of experimental allergic encephalomyelitis in the mouse showed that from strain to strain, the condition was similar. The over-all pathologic picture was somewhat midway between that seen in other species sensitized with whole nervous tissue in complex Freund's adjuvant and hyperacute experimental allergic encephalomyelitis in rats similarly sensitized but with the addition of B. pertussis. Perivascular cuffing, though present, was less pronounced than in other species. There was a prominent polymorphonuclear response, and extravasation of fibrin and red cells occurred. Primary demyelination was a transient, early feature of the disease process in mice, but nerve fiber depletion and gliosis occurred as the disease progressed. The observed myelin degradation most commonly involved the ingestion by macrophages of small fragments of dissociated myelin via crypts or infoldings of the cell surface, at the bases of which were pinocytic, coated vesicles. A similar pattern of myelin breakdown has been described in mouse hepatitis virus encephalomyelitis and multiple sclerosis.
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PMID:Neuropathology of experimental allergic encephalomyelitis in inbred strains of mice. 740 30

Bordetella pertussis and Mycobacterium tuberculosis, routinely used to promote the development of autoimmune disease, were recently reported to also be effective in inducing protection against an autoimmune disease. Thus, we previously demonstrated that SJL/J and (SJL/J x BALB/c)F1 mice that are genetically susceptible to experimental autoimmune encephalomyelitis (EAE) become highly refractory to the induction of the disease following their exposure to B. pertussis and M. tuberculosis. In the present study, the pertussis toxin (PT) from B. pertussis and the purified protein derivative (PPD) of M. tuberculosis, were found to be sufficient to fully protect against EAE and thus may be the major bacterial components responsible for conferring protection. The 65-kDa heat-shock protein played only a marginal role in the protection against EAE induced by these bacteria. Both PT and PPD were protective when given before, but not after, the encephalitogenic challenge, and minute amounts (5-50 ng) emulsified in oil were sufficient to confer long-lasting resistance to EAE. The effect of PT or PPD on EAE differed from that of mitogens or bacterial superantigens, suggesting that their protection ability was not attributable merely to mitogenic or superantigenic properties. The mechanism of protection is not yet clear. Preliminary studies revealed a complex mechanism of protection whereby PPD and PT may operate differently. Thus, only PPD-induced, but not PT-induced, protection was transferrable by CD4+ T lymphocytes bearing an alpha beta T cell antigen receptor. Neither PT nor PPD had a protective effect on EAE mediated by preformed pathogenic T lymphocytes and it is most likely that they exert their protection by affecting the development of such T lymphocytes. How bacteria such as B. pertussis and M. tuberculosis can either enhance the development of an autoimmune disease or protect against the disease is not yet clear. However, identifying PT and PPD as the bacterial components active in protection may allow a better understanding of the modulatory effects of bacteria and point to the potential use of such bacterial products in immunomodulation of autoimmune diseases.
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PMID:Protection against autoimmune disease by bacterial agents. II. PPD and pertussis toxin as proteins active in protecting mice against experimental autoimmune encephalomyelitis. 809 58

Linomide (LS-2616, quinoline-3-carboxamide) is a synthetic immunomodulator that stimulates natural killer cell activity and activates several lymphocytic subpopulations in experimental animals and humans. In this study we determined the effect of oral treatment with linomide on the development of experimental autoimmune encephalomyelitis, an animal model for immune-mediated human demyelinating disorders. Experimental autoimmune encephalomyelitis was induced in SJL/J mice and in an outbred strain of rats (Sabra) by subcutaneous injection of spinal cord homogenate in adjuvant followed by inoculation with Bordetella pertussis. Linomide was administered in drinking water, at an estimated dose of 50 to 100 mg/kg/day. None of the linomide-treated mice (0/41) and Sabra rats (0/15) developed any clinical or pathological signs of experimental autoimmune encephalomyelitis, whereas almost all control animals (48/53 and 18/19, respectively) were severely paralyzed and 64.5% died from the disease. Lymphocytes obtained from linomide-treated animals had reduced in vitro proliferative responses to guinea pig myelin basic protein, proteolipid protein of the myelin, and tuberculin-purified protein derivative, unlike antigen-independent proliferation which was rather unaffected. Natural killer cell activity (tested by a cytotoxic assay on radiolabeled YAC-1 target cells) was significantly enhanced in mice treated with linomide. Our results indicate that modulation of the immune system with linomide leads to complete inhibition of experimental autoimmune encephalomyelitis in the absence of systemic immunosuppression. Linomide could therefore be of use in future clinical trials for the treatment of human autoimmune demyelinating disorders.
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PMID:Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide. 823 57

The histopathological features of uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis (EAE) were investigated using light and electron microscopy. Lewis rats were immunized by spinal cord homogenate, complete Freund's adjuvant and Bordetella pertussis. The eyes of rats with EAE exhibited vasculitis in the iris, trabeculitis and endothelial abnormalities in the retinal vessels; vasculitis was observed in the optic nerve and brain. Endothelial cells in the vessels in the iris, retina, optic nerve and central nervous system were noted to be elevated (high endothelial-like venules, or HELV). Inflammatory cells in the vascular lumen were attached to the surface of endothelial cells in abnormal areas in the iris. By comparison with the findings in the iris and retina, there were no significant changes in the vessels of the ciliary body and choroid. The ultrastructural features indicated that anterior uveitis in acute EAE resulted from vasculitis in the iris due to changes of the endothelial cells and was not due to a reaction against the myelinated nerves or any other particular components of the iris. In addition, our results suggested that vasculitis in the iris was consequent upon specialized changes of the endothelial cells similar to HELV which were responsible for the transcellular emigration of lymphocytes in other inflammatory diseases or in experimental models. HELV change plays an important role in the perivascular inflammatory process in the iris, retina, optic nerve and central nervous system in EAE and possibly in multiple sclerosis.
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PMID:Uveitis and retinal vasculitis in acute experimental allergic encephalomyelitis in the Lewis rat: an ultrastructural study. 815 31

Pertussis toxin (PTX) is the primary component responsible for eliciting the majority of biological activities associated with Bordetella pertussis, including the induction of several tissue-adjuvant models of organ-specific autoimmune disease. PTX, when administered in vivo, enhances vascular permeability, which is made manifest by a concomitant increase in sensitivity to a variety of agents and treatments affecting the vascular bed. One such agent is histamine, and the response to PTX, as measured by hypersensitivity following vasoactive amine challenge, is genetically controlled by the Bphs locus. Susceptibility to the induction of both experimental allergic encephalomyelitis (EAE) and experimental allergic orchitis (EAO) in mice is associated with, and in the latter case linked to, a susceptible allele at this locus. We report here the mapping of the Bphs locus to mouse chromosome 6, telomeric of Tcrb and centromeric of Prp (D6Nds8). This region also contains a number of loci of immunologic relevance including Igk, Ly-2, Ly-3, Il-5r, Ly-35, Ly-4, and Tnfr-2.
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PMID:Locus controlling Bordetella pertussis-induced histamine sensitization (Bphs), an autoimmune disease-susceptibility gene, maps distal to T-cell receptor beta-chain gene on mouse chromosome 6. 847 18

Treatment of SJL mice with 400 ng Bordetella pertussis toxin (PT) either in saline or emulsified in incomplete Freund's adjuvant protected the mice against experimental autoimmune encephalomyelitis (EAE) induced 28 days later by a synthetic peptide of myelin proteolipid protein (PLP139-151) in complete Freund's adjuvant. However, treatment with a genetically inactivated pertussis toxin in which the catalytic and NAD-binding sites of the ADP-ribosyltransferase subunit were modified by site-directed mutagenesis was without effect. In vitro, lymphocyte proliferation was considerably enhanced by both the native and the inactivated toxin, at concentrations of 0.1-1 microgram/ml. However, strong inhibition of proliferation was also observed with the native toxin only, at concentrations that were two to three orders of magnitude lower than that required for the mitogenic effect (0.1-1 ng/ml). The inhibition of proliferation was detectable in the case of high-background proliferation, after stimulation with antigen (PLP139-151) or purified protein derivative of Mycobacterium tuberculosis), or with anti-CD3 monoclonal antibody, but not after stimulation with concanavalin A or phorbol esters and Ca2+ ionophore. These results suggest that the inhibitory effect of PT operates by interfering selectively with a T cell receptor-dependent signaling pathway. The biological significance of the in vitro inhibitory effect of PT was demonstrated by a considerable decrease and/or delay in the ability of lymphocytes grown with PLP139-151 and low concentrations of PT to transfer EAE to naive recipients.
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PMID:Native, but not genetically inactivated, pertussis toxin protects mice against experimental allergic encephalomyelitis. 864 Aug 62

Bordetella pertussis and its major virulence component, pertussis toxin (PT), have been used routinely to promote the development of such murine experimental autoimmune diseases as experimental autoimmune encephalomyelitis (EAE). Recently, we reported that B. pertussis also can protect against EAE. The protective activity was assigned to PT, a complex holomer composed of an A-promoter, the toxic S1 subunit, and a B-oligomer comprised of subunits S2, S3, S4, and S5. Although some data are available to explain how PT can enhance the development of EAE, nothing is known about the mechanism by which it protects against the disease. Toward understanding how PT can have such conflicting effects on EAE, we investigated the immunomodulatory activity of the various components of PT. Herein we show that the enhancing and protective activities reside within different regions of the PT holomer. Thus, though S1 appeared essential in imparting enhancing activity to PT, it played no role of importance in disease protection, and the protective effects of PT could be assigned fully to the B-oligomer. Further investigation with gel-purified PT subunits revealed that B-oligomer subunits protected against EAE to varying extent, with S3 being the most protective. These data suggest a potential therapeutic application for the B-oligomer or some of its subunits, which appear to be potent protective agents, without the toxicity or disease-promoting activity associated with PT.
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PMID:Immunomodulation of murine experimental autoimmune encephalomyelitis by pertussis toxin: the protective activity, but not the disease-enhancing activity, can be attributed to the nontoxic B-oligomer. 906 80

Experimental autoimmune encephalomyelitis in the common marmoset, a nonhuman primate species (Callithrix jacchus), is a new model for multiple sclerosis. Given the close immunological relationship between marmosets and humans, it is an attractive model for investigating immunopathological pathways relevant to multiple sclerosis and to evaluate new treatments for the disease. Unlike in the originally documented model, experimental autoimmune encephalomyelitis induced without the use of Bordetella pertussis led to a chronic disease of moderate severity. The clinical course of experimental autoimmune encephalomyelitis in the present model was mainly chronic and progressive, but periods of incomplete remission did occur. At the chronic stage of the disease, actively demyelinating lesions were found together with inactive demyelinated and remyelinated (shadow) plaques. Before immunization and during clinically active experimental autoimmune encephalomyelitis, T1- and T2-weighted magnetic resonance brain images were obtained. Correlation of the data from the magnetic resonance images and the neuropathology analysis revealed that the hyperintense regions in T2-weighted images represented both active and inactive remyelinating lesions. Quantification showed that the number of lesions in T2-weighted magnetic resonance images equalled those found by pathological examination, and thus T2-weighted magnetic resonance imaging can be used to discern the total lesion load. Extravasation of gadolinium-diethylenetriamine-penta-acetic acid (triple dose) was found only in lesions, which by histopathology were shown to be engaged in the process of active demyelination.
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PMID:Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus). 970 23

Experimental autoimmune encephalomyelitis (EAE) is an inducible autoimmune disease widely used as a model of the acute/relapsing stage of multiple sclerosis. We have previously shown that treatment of EAE-mice with high doses of cyclophosphamide (CY) (350 mg kg), followed by syngeneic bone marrow transplantation (SBMT), completely abrogates the clinical paralytic signs and even prevents the appearance of new relapses in the chronic-relapsing model of the disease. In the present study we examined whether this treatment protocol induces long term tolerance and whether this tolerance is antigen-specific. EAE was induced by immunization with spinal cord homogenate (MSCH) in complete Freund's adjuvant (CFA). The treatment with CY and SBMT was performed on day 6 post immunization. Treated and untreated mice were rechallenged with MSCH, or a non-relevant antigen (OVA) in CFA at various stages after the first paralytic attack. In contrast to previous data showing that animals recovering from acute EAE are usually refractory to re-induction of the disease, repeated injections of MSCH at different sites from the initial immunization, followed by i.v. injection of inactivated Bordetella bacteria, 2, 4 and 6 months after the initial EAE-induction, caused a severe and usually lethal relapse in all the untreated, control animals. Mice treated with CY and SBMT were resistant to all rechallenges with the same encephalitogenic inoculum. Following the second rechallenge, peripheral lymph node cells were examined in vitro for their proliferative responses to myelin antigens or to OVA. Lymphocytes obtained from CY+SBMT treated mice did not proliferate in vitro in response to myelin basic protein (MBP), but proliferated against OVA, when immunized with this antigen, after SBMT. Adoptive transfer of lymphocytes from tolerant mice to naive recipients did not transfer resistance to EAE-induction. Our results indicate that high doses of CY, followed by SBMT, induce long term antigen-specific tolerance presumably by a mechanism of clonal deletion or anergy.
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PMID:Acute/relapsing experimental autoimmune encephalomyelitis: induction of long lasting, antigen-specific tolerance by syngeneic bone marrow transplantation. 1009 98


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