CSF and serum levels of soluble fractalkine (CX3CL1) in inflammatory diseases of the nervous system

Kastenbauer, Stefan; Koedel, Uwe; Wick, Manfred; Kieseier, Bernd C.; Hartung, Hans‐Peter; Pfister, Hans‐Walter

doi:10.1016/s0165-5728(03)00085-7

Cited by 81 publications

(67 citation statements)

References 35 publications

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“…45 In patients with autoimmune disorders, serum levels of fractalkine correlate with disease activity. [22][23][24] Given that the cellular immune response to MBP in spleen and circulating fractalkine levels were correlated in our study, it suggests that this chemokine could also be used as a marker of ongoing inflammation in the brain. Further studies to compare the histological expression of fractalkine and the cellular immune response in brain (ie, influx of lymphocytes) with circulating fractalkine levels and the Th1 response to brain are warranted.…”

Section: Discussionmentioning

confidence: 62%

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Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After Stroke

Gee

Kalil

Thullbery

et al. 2008

Stroke

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Background and Purpose-Animals subjected to an inflammatory insult at the time of stroke are predisposed to the development of an inflammatory autoimmune response to brain. This response is associated with worse neurological outcome. Because induction of immunologic tolerance to brain antigens before stroke onset is associated with improved outcome, we sought to determine whether this paradigm could prevent the deleterious autoimmune response to brain provoked by an inflammatory stimulus at the time of ischemia. Methods-Male Lewis rats were tolerized to myelin basic protein (MBP) or ovalbumin by intranasal administration before middle cerebral artery occlusion. At the time of reperfusion, all animals received lipopolysaccharide (1 mg/kg intraperitoneal). Behavioral tests were performed at set time intervals. Results-One month after middle cerebral artery occlusion, lymphocytes from the spleens of MBP-tolerized animals were less likely to evidence an autoimmune response and more likely to evidence a regulatory response (TREG) toward MBP than those from ovalbumin-tolerized animals. Animals that had an inflammatory response toward MBP (a TH1 response) performed worse on behavioral tests than those that did not. Fractalkine, a surrogate marker of inflammation, was elevated in animals with a TH1 response to MBP. Conclusions-These data extend our previous findings and suggest that deleterious autoimmunity to brain antigens can be prevented by prophylactically inducing regulatory T-cell responses to those antigens.

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Section: Discussionmentioning

confidence: 62%

“…We also assessed serological markers of the immune response, including antibodies to MBP and systemic levels of fractalkine, because the amount of this chemokine in circulation appears to correlate with disease activity in patients with autoimmune disorders. [22][23][24] …”

mentioning

confidence: 99%

Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After Stroke

Gee

Kalil

Thullbery

et al. 2008

Stroke

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“…It is converted to a soluble form on cleavage from the plasma membrane through the action of metalloproteinases, like a disintegrin and metalloproteinase domains (ADAM) 10 and ADAM17 on leukocytes (Hundhausen et al, 2003) or cathepsin S in the spinal cord (Clark et al, 2007). CX3CL1 is constitutively expressed in the nervous system, but levels in the brain can be modulated under diverse pathological conditions (Pan et al, 1997;Hughes et al, 2002;Kastenbauer et al, 2003;Sunnemark et al, 2005;Huang et al, 2006). The presence and the stimulation (Zujovic et al, 2000(Zujovic et al, , 2001Mizuno et al, 2003;Cardona et al, 2006;Lyons et al, 2009) of the CX3CL1 receptor CX3CR1 has been correlated with a reduced release of interleukin-1-b (IL-1-b) and tumor necrosis factor-a (TNF-a) from microglial cells and a lower rate of neuronal degeneration in different experimental models of neuropathologies such as experimental autoimmune encephalomyelitis, 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride striatal injection, lipopolysaccharide administration, and superoxide dismutase (SOD1) mutation (Huang et al, 2006;Cardona et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Lauro

Cipriani

Catalano

et al. 2010

Neuropsychopharmacol

110

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Fractalkine/CX3CL1 is a neuron-associated chemokine, which modulates microglia-induced neurotoxicity activating the specific and unique receptor CX3CR1. CX3CL1/CX3CR1 interaction modulates the release of cytokines from microglia, reducing the level of tumor necrosis factor-a, interleukin-1-b, and nitric oxide and induces the production of neurotrophic substances, both in vivo and in vitro. We have recently shown that blocking adenosine A 1 receptors (A 1 R) with the specific antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) abolishes CX3CL1-mediated rescue of neuronal excitotoxic death and that CX3CL1 induces the release of adenosine from microglia. In this study, we show that the presence of extracellular adenosine is mandatory for the neurotrophic effect of CX3CL1 as reducing adenosine levels in hippocampal cultures, by adenosine deaminase treatment, strongly impairs CX3CL1-mediated neuroprotection. Furthermore, we confirm the predominant role of microglia in mediating the neuronal effects of CX3CL1, because the selective depletion of microglia from hippocampal cultures treated with clodronate-filled liposomes causes the complete loss of effect of CX3CL1. We also show that hippocampal neurons obtained from A 1 R À/À mice are not protected by CX3CL1 whereas A 2A R À/À neurons are. The requirement of functional A 1 R for neuroprotection is not unique for CX3CL1 as A 1 R À/À hippocampal neurons are not rescued from Glu-induced cell death by other neurotrophins such as brain-derived neurotrophic factor and erythropoietin, which are fully active on wt neurons.

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“…In inflamed local organs, such as the liver, lungs, and the kidneys, the participation of fractalkine has been recently noted [35][36][37][38][39][40] . Furthermore, increased s-fractalkine serum levels have been reported for patients with various chronic inflammatory diseases [40][41][42][43][44] . However, until now, there are no reports related to fractalkine in pancreatic inf lammator y diseases.…”

mentioning

confidence: 99%

Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans

Yasuda¹,

Ito²,

Oono³

et al. 2008

WJG

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AIM:To clarify whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis (CP). This study aimed at clarifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CP. METHODS: Serum monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-β1), and soluble type fractalkine (s-fractalkine) concentrations were examined in patients with CP (n = 109) and healthy controls (n = 116). Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specific various clinical factors and serum MCP-1, TGF-β1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude influence of alcohol intake. RESULTS: Patients with CP showed significant higher levels of serum TGF-β1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-β1 in the severe stage and s-fractalkine in the mild and the severe stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-β1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-β1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed significant increase in the early stage of CP. CONCLUSION: It is suggested that the measurement of serum F-fractalkine is useful to diagnose earlystage CP. Moreover, the combined determination of both, s-fractalkine and TGF-β1, in human sera may be helpful in evaluating the severity status of CP.

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CSF and serum levels of soluble fractalkine (CX3CL1) in inflammatory diseases of the nervous system

Cited by 81 publications

References 35 publications

Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After Stroke

Induction of Immunologic Tolerance to Myelin Basic Protein Prevents Central Nervous System Autoimmunity and Improves Outcome After Stroke

Adenosine A1 Receptors and Microglial Cells Mediate CX3CL1-Induced Protection of Hippocampal Neurons Against Glu-Induced Death

Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans

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