Cytokine accumulations in CSF of multiple sclerosis patients

Hauser, S L; Doolittle, Teresa H.; Lincoln, Robin; Brown, R. H.; Dinarello, Charles A.

doi:10.1212/wnl.40.11.1735

Cited by 255 publications

(100 citation statements)

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“…Consistently, in the present study, CSF IL-6 was elevated in acute NBD as well as in CP NBD, but not in non-NBD. Previous studies demonstrated that CSF IL-6 was not elevated in patients with multiple sclerosis [22, 23]. Therefore, the determination of CSF IL-6 might be useful for the differential diagnosis of NBD and multiple sclerosis.…”

Section: Discussionmentioning

confidence: 98%

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

et al. 2011

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To delineate the clinical characteristics of neuro-Behçet’s disease (NBD), a multicenter retrospective survey was performed in BD patients who had presented any neurological manifestations between 1988 and 2008. The diagnosis of acute NBD, chronic progressive (CP) NBD, and non-NBD was confirmed by retrospective review of clinical records. Data on a total of 144 patients were collected; 76 with acute NBD, 35 with CP NBD, and 33 with non-NBD. High-intensity lesions on T2-weighted magnetic resonance imaging (MRI) were found in 60.5% of the patients with acute NBD, 54.2% with CP NBD, and 42.4% with non-NBD, whereas brainstem atrophy was observed in 7.5% with acute NBD, 71.4% with CP NBD, and 9.0% with non-NBD. The cerebrospinal fluid (CSF) cell count was prominently elevated in patients with acute NBD, but was normal in about 15% of those with CP NBD. The sensitivity and specificity of the CSF cell count for the diagnosis of acute NBD versus non-NBD were 97.4 and 97.0%, respectively (cut-off 6.2/mm3). The sensitivity and specificity of CSF interleukin (IL)-6 for the diagnosis of CP NBD versus the recovery phase of acute NBD were 86.7 and 94.7%, respectively (cut-off 16.55 pg/ml). The results indicate that elevation of the CSF cell count and CSF IL-6 and the presence of brainstem atrophy on MRI are useful for the diagnosis of NBD.

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Section: Discussionmentioning

confidence: 98%

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

et al. 2011

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“…Interestingly, the proinflammatory cytokine IL-1␤ enhances P2X 7 receptor expression and function in astrocytes (Narcisse et al, 2005). Thus, increased levels of IL-1␤ in MS and its animal model EAE (Hauser et al, 1990) can intensify signaling through the P2X 7 receptor and lead to the release of ATP and glutamate, which causes oligodendrocyte excitotoxicity. This may be relevant to the progression of tissue damage in normal-appearing white matter in MS because, in the chronic state of the disease, diffuse inflammation accumulates throughout the whole brain and is associated with slowly progressive axonal injury (Kutzelnigg et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

Matute¹,

Torre²,

et al. 2007

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Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS).Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X 7 purinergic receptors expressed by these cells. Sustained activation of P2X 7 receptors in vivo causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X 7 antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X 7 activation and that this cell death process contributes to EAE. Importantly, P2X 7 expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X 7 receptor antagonists may be beneficial for the treatment of MS.

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“…Indeed, positive correlations have been observed between the degree of neuronal death during bacterial meningitis and the levels of TNF-a, IL-1b and IL-1R2. [12][13][14][15] Moreover, TNF-a concentrations are higher than normal in multiple sclerosis (MS) patients 16 and in Alzheimer's patients, 17 while TNF-a and IL-1b levels are increased in those afflicted by Parkinson's disease. 18 Moreover, TNF-a KO mice are protected against neuronal death in models of Parkinson's disease.…”

Section: Innate Immunity and The Central Nervous Systemmentioning

confidence: 99%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the b-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

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Cytokine accumulations in CSF of multiple sclerosis patients

Cited by 255 publications

References 0 publications

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

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Cytokine accumulations in CSF of multiple sclerosis patients

Cited by 255 publications

References 0 publications

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

Clinical characteristics of neuro-Behcet’s disease in Japan: a multicenter retrospective analysis

P2X7Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Contact Info

Product

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P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis