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

---

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

It is claimed that interferon-tau (IFN-tau) has broad cross-species reactivity and less cytotoxicity than other type I IFN when used at high concentration either in vitro or in living animals. It can also amelioriate the development of experimental allergic encephalomyelitis (EAE) without the usual side effects of IFN therapy in mice autoimmunized with myelin basic protein. For these reasons, IFN-tau may have therapeutic potential in humans. Here, the antiviral (AV) activities of eight different recombinant IFN-tau were compared with those of several bovine, human, and murine type I IFN on bovine MDBK cells, murine L929 cells, and human WISH cells. The data show that only one of the IFN-tau, OvIFN-tau4, has broad cross-species reactivity. It was comparable in this respect to HuIFN-omega1 and HuIFN-alpha1. The other IFN-tau, including the variant form (OvIFN-tau1mod) tested by others in cytotoxicity experiments and for its ability to protect mice against EAE, had relatively weak AV activity on mouse and human cells. It is possibly because this particular bioengineered form of IFN-tau binds the common type I receptor of these two species with such low affinity that it lacks cytotoxic effects. The basis for its potent anti-EAE activity is unclear, but it seems possible that it does not involve the type I IFN receptor.
...
PMID:The cross-species antiviral activities of different IFN-tau subtypes on bovine, murine, and human cells: contradictory evidence for therapeutic potential. 1063 2

Dynamic interplay between cytokines and chemokines directs trafficking of leukocyte subpopulations to tissues in autoimmune inflammation. We have examined the role of IFN-gamma in directing chemokine production and leukocyte infiltration to the CNS in experimental autoimmune encephalomyelitis (EAE). BALB/c and C57BL/6 mice are resistant to induction of EAE by immunization with myelin basic protein. However, IFN-gamma-deficient (BALB/c) and IFN-gammaR-deficient (C57BL/6) mice developed rapidly progressing lethal disease. Widespread demyelination and disseminated leukocytic infiltration of spinal cord were seen, unlike the focal perivascular infiltrates in SJL/J mice. Gr-1+ neutrophils predominated in CNS, and CD4+ T cells with an activated (CD69+, CD25+) phenotype and eosinophils were also present. RANTES and macrophage chemoattractant protein-1, normally up-regulated in EAE, were undetectable in IFN-gamma- and IFN-gammaR-deficient mice. Macrophage inflammatory protein-2 and T cell activation gene-3, both neutrophil-attracting chemokines, were strongly up-regulated. There was no induction of the Th2 cytokines, IL-4, IL-10, or IL-13. RNase protection assays and RT-PCR showed the prevalence of IL-2, IL-3, and IL-15, but no increase in IL-12p40 mRNA levels in IFN-gamma- or IFN-gammaR-deficient mice with EAE. Lymph node cells from IFN-gamma-deficient mice proliferated in response to myelin basic protein, whereas BALB/c lymph node cells did not. These findings show a regulatory role for IFN-gamma in EAE, acting on T cell proliferation and directing chemokine production, with profound implications for the onset and progression of disease.
...
PMID:IFN-gamma shapes immune invasion of the central nervous system via regulation of chemokines. 1067 18

The perivascular transmigration and accumulation of macrophages and T lymphocytes in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) may be partly regulated by low m.w. chemotactic cytokines. Using the RNase protection assay and ELISA, we quantified expression of chemokines and chemokine receptors in the spinal cord (SC), brain, and lymph nodes of BV8S2 transgenic mice that developed or were protected from EAE by vaccination with BV8S2 protein. In paralyzed control mice, the SC had increased cellular infiltration and strong expression of the chemokines RANTES, IFN-inducible 10-kDa protein, and monocyte chemoattractant protein-1 and the cognate chemokine receptors CCR1, CCR2, and CCR5, with lower expression of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2; whereas brain had less infiltration and a lower expression of a different pattern of chemokines and receptors. In TCR-protected mice, there was a decrease in the number of inflammatory cells in both SC and brain. In SC, the reduced cellular infiltrate afforded by TCR vaccination was commensurate with profoundly reduced expression of chemokines and their cognate chemokine receptors. In brain, however, TCR vaccination did not produce significant changes in chemokine expression but resulted in an increased expression of CCR3 and CCR4 usually associated with Th2 cells. In contrast to CNS, lymph nodes of protected mice had a significant increase in expression of MIP-2 and MIP-1beta but no change in expression of chemokine receptors. These results demonstrate that TCR vaccination results in selective reduction of inflammatory chemokines and chemokine receptors in SC, the target organ most affected during EAE.
...
PMID:Reduced chemokine and chemokine receptor expression in spinal cords of TCR BV8S2 transgenic mice protected against experimental autoimmune encephalomyelitis with BV8S2 protein. 1072 56

Given the critical role of cytokines in the regulation of an inflammatory response, we investigated whether certain cytokines are expressed in the brains of normal mice during maturation that could contribute to the immune-privileged nature of the CNS or potentially influence an immune-mediated illness such as experimental allergic encephalomyelitis. The gene expression of IFN gamma (Th1 cytokine) and IL-4 (Th2 cytokine) was analyzed in the brain of several strains of mice. IFN gamma was not detectable. However, IL-4 was present in the brains of neonatal mice, but not adult mice. Resident CNS cells are believed to be the source of the IL-4, because mice deficient in T cells (SCID and RAG2-/-) expressed the IL-4 gene in the CNS. Further analysis indicated that the gene expression of the Th2 cytokine transcription factor, GATA-3, correlated with IL-4 and IL-10 expression in the brain. Since GATA-3-deficient mice have an abnormal CNS, brain-derived Th2 cytokines may play an important role in CNS development, as well as potentially contribute to the immune-privileged nature of the brain.
...
PMID:Developmentally regulated gene expression of Th2 cytokines in the brain. 1086 98

The contribution of the T cell chemoattractant chemokine IFN-inducible protein 10 (IP-10) in host defense following viral infection of the CNS was examined. IP-10 is expressed by astrocytes during acute encephalomyelitis in mouse hepatitis virus-infected mice, and the majority of T lymphocytes infiltrating into the CNS expressed the IP-10 receptor CXCR3. Treatment of mice with anti-IP-10 antisera led to increased mortality and delayed viral clearance from the CNS as compared with control mice. Further, administration of anti-IP-10 led to a >70% reduction (p </= 0.001) in CD4+ and CD8+ T lymphocyte infiltration into the CNS, which correlated with decreased (p </= 0.01) levels of IFN-gamma. These data indicate that IP-10 functions as a sentinel molecule in host defense and is essential in the development of a protective Th1 response against viral infection of the CNS.
...
PMID:The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease. 1094 53

Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a chronic demyelinating disease with clinical and histological similarities with the human demyelinating disease multiple sclerosis (MS). Following MHV infection, chemokines including CXC chemokine ligand (CXCL)10 (IFN inducible protein 10 kDa), CXCL9 (monokine induced by IFN-gamma), and CC chemokine ligand 5 (RANTES) are expressed during both acute and chronic stages of disease suggesting a role for these molecules in disease exacerbation. Previous studies have shown that during the acute phase of infection, T lymphocytes are recruited into the CNS by the chemokines CXCL10 and CXCL9. In the present study, MHV-infected mice with established demyelination were treated with antisera against these two chemokines, and disease severity was assessed. Treatment with anti-CXCL10 reduced CD4+ T lymphocyte and macrophage invasion, diminished expression of IFN-gamma and CC chemokine ligand 5, inhibited progression of demyelination, and increased remyelination. Anti-CXCL10 treatment also resulted in an impediment of clinical disease progression that was characterized by a dramatic improvement in neurological function. Treatment with antisera against CXCL9 was without effect, demonstrating a critical role for CXCL10 in inflammatory demyelination in this model. These findings document a novel therapeutic strategy using Ab-mediated neutralization of a key chemokine as a possible treatment for chronic human inflammatory demyelinating diseases such as MS.
...
PMID:Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis. 1156 31

Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99% of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.
...
PMID:Preservation of motor function by inhibition of CD8+ virus peptide-specific T cells in Theiler's virus infection. 1160 79

The clinical and histological picture and immunocytochemical expression of some cytokines on infiltrates in the central nervous system of Lewis rats were studied in adult rats in the course of short-term therapy of acute experimental allergic encephalomyelitis with interferon beta 1a (IFN beta 1a). There was established the beneficial effect of the short-term treatment of EAE with IFN beta 1a, applied at the early onset of the experimental disease. The effect of IFN beta 1a on EAE seems likely to be associated with the inhibition of proinflammatory cytokines and stimulation of anti-inflammatory ones.
...
PMID:The effect of short-term treatment with interferon beta 1a on acute experimental allergic encephalomyelitis. 1168 Jun 40

Interferon-tau (IFN-tau) is a member of the type I IFN family. Although its distribution is restricted to ruminants, IFN-tau is active against cells of humans and mice. It has been reported that oral administration of ovine IFN-tau (OvIFN-tau) prevents both acute and chronic relapsing forms of murine experimental allergic encephalomyelitis (EAE). Here, we examined the effect in mice of peroral gastric administration of OvIFN-tau on the induction of 2',5'-oligoadenylate synthetase (OAS) activity in whole blood. Before administration, mice were deprived of food and drink for 6 h, and IFN was given by either intraperitoneal (i.p.) injection or per-oral gastric administration. When administered gastrically, IFN was introduced directly into the upper part of the stomach using an oral feeding needle. OAS activity in whole blood increased dependent on dose (0-105 U) and time (0-24 h), with no significant difference in the level of activity between the two routes. An increase in the activity of OAS in blood following administration of OvIFN-tau was observed in ICR, BALB/c, C57BL/6, NZW/N, and SJL/J mice, although the extent of the increase varied with the strain. Blood OAS levels also increased on administration of murine IFN-alpha (MuIFN-alpha). However, higher levels were detected after i.p. injection than after gastric administration.
...
PMID:Induction of blood 2',5'-oligoadenylate synthetase activity in mice by gastric administration of ovine IFN-tau. 1203 48

IFN-tau, a novel type I IFN that possesses immunomodulatory properties, lacks toxicity normally associated with other type I IFNs. We examined the effects of oral IFN-tau alone and in combination with oral glatiramer acetate in experimental allergic encephalomyelitis (EAE). By comparison of oral administration of IFN-alpha, -beta, and -tau to myelin basic protein-specific TCR-transgenic mice, we demonstrate these type I IFNs promote secretion of the Th2 cytokine IL-10 with similar efficiency. Whereas IFN-alpha and -beta induced IFN-gamma secretion, a Th1 cytokine, IFN-tau did not. Oral IFN-tau alone suppressed EAE. When suboptimal doses were administered orally in combination to wild-type mice, IFN-tau and glatiramer acetate had a synergistic beneficial effect in suppression of EAE. This combination was associated with TGF-beta secretion and enhanced IL-10 production. Thus, IFN-tau is a potential candidate for use as a single agent or in combination therapy for multiple sclerosis.
...
PMID:Cutting edge: oral type I IFN-tau promotes a Th2 bias and enhances suppression of autoimmune encephalomyelitis by oral glatiramer acetate. 1219 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---