Abstract | BACKGROUND: METHODS: RESULTS: TNF was specifically sustained in infiltrating macrophages. Anti-TNF treatment decreased established clinical disability and mortality rate within 7 days. Control of disease progression was associated with a decline in myelin loss and leukocyte infiltration, as well as macrophage activation. In addition to mitigating CNS inflammation, TNF neutralization restored BBB integrity and enhanced CNS anti-inflammatory responses. CONCLUSIONS: Sustained TNF production by infiltrating macrophages associated with progressive EAE exacerbates disease severity by promoting inflammation and disruption of BBB integrity, thereby counteracting establishment of an anti-inflammatory environment required for disease remission.
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Authors | Alice Valentin-Torres, Carine Savarin, David R Hinton, Timothy W Phares, Cornelia C Bergmann, Stephen A Stohlman |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 13
Pg. 46
(Feb 22 2016)
ISSN: 1742-2094 [Electronic] England |
PMID | 26906225
(Publication Type: Journal Article)
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Chemical References |
- Aif1 protein, mouse
- Antibodies
- Antigens, CD
- Calcium-Binding Proteins
- Glial Fibrillary Acidic Protein
- Microfilament Proteins
- Myelin-Oligodendrocyte Glycoprotein
- Peptide Fragments
- Tumor Necrosis Factor-alpha
- myelin oligodendrocyte glycoprotein (35-55)
- Interferon-gamma
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Topics |
- Animals
- Antibodies
(pharmacology)
- Antigens, CD
(metabolism)
- Blood-Brain Barrier
(physiopathology)
- Calcium-Binding Proteins
(metabolism)
- Capillary Permeability
(genetics)
- Central Nervous System
(pathology)
- Disease Models, Animal
- Encephalomyelitis, Autoimmune, Experimental
(chemically induced, pathology)
- Gene Expression Regulation
(genetics)
- Glial Fibrillary Acidic Protein
(genetics, metabolism)
- Humans
- Interferon-gamma
(genetics, metabolism)
- Macrophages
(metabolism)
- Mice
- Mice, Transgenic
- Microfilament Proteins
(metabolism)
- Myelin-Oligodendrocyte Glycoprotein
(toxicity)
- Neuroglia
(pathology)
- Neutrophil Infiltration
(drug effects, genetics)
- Peptide Fragments
(toxicity)
- Tumor Necrosis Factor-alpha
(immunology, metabolism)
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