Intrathecal release of pro- and anti-inflammatory cytokines during stroke

Tarkowski, E; Rosengren, Lars; Blomstrand, Christian; Wikkelsø, Carsten; Jensen, Christer; Ekholm, Sven; Tarkowski, Andrzej

doi:10.1046/j.1365-2249.1997.4621483.x

Cited by 198 publications

(168 citation statements)

References 29 publications

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“…The increased levels of IL-8 in CSF in patients with short duration of sciatic pain in the present study indicate an early inflammatory response, which most likely decreases after a couple of months, whereafter there are no signs of elevated IL-8 (or other cytokines). The concentrations of IL-8 in CSF found in our study (mean, 57±65 pg/ml) are comparable to the concentrations in CSF and serum from healthy subjects and stroke patients in a study by Tarkowski and coworkers [27]. The mean IL-8 concentration in CSF in the control subjects was 25 pg/ml; the stroke patients showed a mean of 85 pg/ml at day 2 after onset, which decreased thereafter.…”

Section: Discussionsupporting

confidence: 86%

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica

et al. 2001

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Section: Discussionsupporting

confidence: 86%

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica

et al. 2001

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“…47 In addition, the IL-8 chemokine has also been associated with the recruitment of inflammatory cells and is increased in stroke patients. 48,49 It has been associated with amplification of the secondary inflammatory process following stroke. 50,51 Finally, emerging data indicate that the cytokine IL-18, which seems to play a key role in neuroinflammation and neurodegeneration, is able to mediate delayed neuroinflammatory processes in experimental hypoxic-ischemic brain injury and is involved in stroke-induced neuroinflammation in humans (reviewed by Felderholf-Mueser et al 52 ).…”

Section: Resultsmentioning

confidence: 99%

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

et al. 2006

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Although poststroke depression is unlikely to represent a single disorder and numerous etiologies for different kinds of poststroke depression will likely emerge as the result of future research, we believe that a number of poststroke depressive disorders are likely to be the result of specific changes in brain pathology and neurophysiology. Nevertheless, there are relatively few hypotheses about the pathophysiology of poststroke depression. This paper, therefore, proposes a new hypothesis for poststroke depression involving increased production of proinflammatory cytokines resulting from brain ischemia in cerebral areas linked to the pathogenesis of mood disorders. This paper reviews the evidence supporting the hypothesis that proinflammatory cytokines are involved in the occurrence of stroke as well as mood disorders linked to the brain damage. The increased production of proinflammatory cytokines such as IL-1b, TNF-a or IL-18 resulting from stroke may lead to an amplification of the inflammatory process, particularly in limbic areas, and widespread activation of indoleamine 2,3-dioxygenase (IDO) and subsequently to depletion of serotonin in paralimbic regions such as the ventral lateral frontal cortex, polar temporal cortex and basal ganglia. The resultant physiological dysfunction may lead to poststroke depression. Future investigations may explore this hypothesis through more extensive studies on the role of proinflammatory cytokines, such as IL-1b, TNF-a or even IL-18, in patients with poststroke depression. Molecular Psychiatry (2006) 11, 984-991.

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“…That both fetal and adult human astrocytes can be activated by IL-1␤ to express IL-8 and IP-10 has been well established (Oh et al, 1999;Hua and Lee, 2000). IL-8 is an ELR-positive (i.e., Glu-Leu-Arg motif-containing) ␣ chemokine that is principally recognized for its role as a chemotactic factor for neutrophils (Yasumoto et al, 1992), and levels of IL-8 rise dramatically in the CSF of patients with bacterial meningitis (Spanaus et al, 1997), as well as after brain injury, ischemia, and stroke (Tarkowski et al, 1997;Whalen et al, 2000). IL-8 may also play other roles in the CNS because it has been shown to provide trophic support for specific neuronal populations against a variety of toxic insults (Bruno et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

John¹,

Simpson

Woodroofe

et al. 2001

J. Neurosci.

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The cytokine interleukin-1␤ (IL-1␤) is a potent activator of human astrocytes, inducing or modulating expression of multiple proinflammatory genes via activation of the transcription factors nuclear factor-B (NF-B) and activator protein-1 (AP-1). In this study, we examined whether IL-1␤ signaling is regulated in these cells by extracellular nucleotides that are released at high concentrations under inflammatory conditions and act as ligands for members of the P2 receptor family. Using reporter constructs and electromobility shift assays, we found that cotreatment of astrocyte cultures with ATP (1-100 M) significantly potentiated IL-1␤-mediated activation of NF-B and AP-1 and that ATP alone activated AP-1. These effects were blocked by the P2 receptor antagonists XAMR 0721, periodate-oxidized ATP, and suramin. A role for ATP in modulating IL-1␤-mediated inflammatory gene expression was supported further by the observation that ATP potentiated the IL-1␤-induced expression of IL-8 mRNA and protein but strongly downregulated IP-10 expression. Reverse transcription-PCR and cloning demonstrated expression of the ATP-responsive P2 receptor subtypes P2Y 1 , P2Y 2 , and P2X 7 , as well as the ATP-insensitive receptor P2Y 4 . ADP, a selective agonist for P2Y 1 , produced results similar to or greater than those obtained using ATP, whereas 2Ј-3Ј-O-(4-benzoylbenzoyl)-ATP, a selective agonist for P2X 7 , was less effective than ATP. In contrast, UTP, a selective agonist for P2Y 2 and P2Y 4 , was ineffective. These studies indicate that different P2 receptor subtypes play distinct roles in the modulation of IL-1␤-mediated signal transduction in human astrocytes, and that signaling via P2 receptors may fine-tune the transcription of genes involved in inflammatory responses in the human CNS.

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Intrathecal release of pro- and anti-inflammatory cytokines during stroke

Cited by 198 publications

References 29 publications

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica

Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica

The etiology of poststroke depression: a review of the literature and a new hypothesis involving inflammatory cytokines

Extracellular Nucleotides Differentially Regulate Interleukin-1β Signaling in Primary Human Astrocytes: Implications for Inflammatory Gene Expression

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