Linked Life Data

12707359

Source:http://linkedlifedata.com/resource/pubmed/id/12707359

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-4-22
pubmed:abstractText
Since the basic mechanisms behind the beneficial effects of IFN-beta in multiple sclerosis (MS) patients are still obscure, here we have investigated the effects of IFN-beta gene disruption on the commonly used animal model for MS, experimental autoimmune encephalomyelitis (EAE). We show that IFN-beta knockout (KO) mice are more susceptible to EAE than their wild-type (wt) littermates; they develop more severe and chronic neurological symptoms with more extensive CNS inflammation and demyelination. However, there was no discrepancy observed between wt and KO mice regarding the capacity of T cells to proliferate or produce IFN-gamma in response to recall Ag. Consequently, we addressed the effect of IFN-beta on encephalitogenic T cell development and the disease initiation phase by passive transfer of autoreactive T cells from KO or wt littermates to both groups of mice. Interestingly, IFN-beta KO mice acquired a higher incidence and augmented EAE regardless of the source of T cells. This shows that the anti-inflammatory effect of endogenous IFN-beta is predominantly exerted on the effector phase of the disease. Histopathological investigations of CNS in the effector phase revealed an extensive microglia activation and TNF-alpha production in IFN-beta KO mice; this was virtually absent in wt littermates. This coincided with an increase in effector functions of T cells in IFN-beta KO mice, as measured by IFN-gamma and IL-4 production. We suggest that lack of endogenous IFN-beta in CNS leads to augmented microglia activation, resulting in a sustained inflammation, cytokine production, and tissue damage with consequent chronic neurological deficits.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4776-84
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12707359-Adjuvants, Immunologic, pubmed-meshheading:12707359-Adoptive Transfer, pubmed-meshheading:12707359-Animals, pubmed-meshheading:12707359-Autoantibodies, pubmed-meshheading:12707359-Autoantigens, pubmed-meshheading:12707359-Cells, Cultured, pubmed-meshheading:12707359-Chronic Disease, pubmed-meshheading:12707359-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:12707359-Gene Deletion, pubmed-meshheading:12707359-Genetic Predisposition to Disease, pubmed-meshheading:12707359-Immunophenotyping, pubmed-meshheading:12707359-Incidence, pubmed-meshheading:12707359-Inflammation, pubmed-meshheading:12707359-Interferon-beta, pubmed-meshheading:12707359-Macrophage Activation, pubmed-meshheading:12707359-Mice, pubmed-meshheading:12707359-Mice, Inbred C57BL, pubmed-meshheading:12707359-Mice, Knockout, pubmed-meshheading:12707359-Myelin Basic Proteins, pubmed-meshheading:12707359-Myelin Sheath, pubmed-meshheading:12707359-Peptide Fragments, pubmed-meshheading:12707359-Severity of Illness Index, pubmed-meshheading:12707359-T-Lymphocyte Subsets, pubmed-meshheading:12707359-Th1 Cells, pubmed-meshheading:12707359-Th2 Cells
pubmed:year
2003
pubmed:articleTitle
IFN-beta gene deletion leads to augmented and chronic demyelinating experimental autoimmune encephalomyelitis.
pubmed:affiliation
Section for Medical Inflammation Research, Department of Cell and Molecular Biology, University of Lund, Lund, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't