Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production

Emsley, Hedley; Smith, Craig J.; Gavin, C; Georgiou, Rachel; Vail, Andy; Barberan, Elisa M.; Illingworth, K.; Scarth, Sylvia; Wickramasinghe, Vijitha; Hoadley, Margaret E.; Rothwell, Nancy J.; Tyrrell, Pippa J.; Hopkins, Stephen J.

doi:10.1186/1471-2377-7-5

Cited by 79 publications

(65 citation statements)

References 43 publications

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“…Our preliminary trial of IL-1RA in stroke patients supports this view in that it showed a reduction in plasma IL-6, as well as C-reactive protein and the leukocyte cell count (Emsley et al, 2005). Since the most likely source of increased plasma IL-6 after stroke is the central nervous system (Emsley et al, 2007), this suggests that IL-1RA has an impact on IL-6 induction in the brain. Although our trial in stroke hinted at clinical efficacy, it was too small to provide sufficient evidence of this.…”

Section: Discussionsupporting

confidence: 65%

“…Growing evidence implicates inflammation and inflammatory molecules such as interleukin (IL)-1 in central nervous system disease (Lipton, 1999;Ginsberg, 2002;Allan and Rothwell, 2003;Lees et al, 2006;Emsley et al, 2007). This cytokine is induced rapidly in response to experimental brain insults and, when administered to rodents centrally or peripherally, enhances brain injury (Rothwell et al, 1997a, b;Allan et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

Clark

McMahon

Gueorguieva

et al. 2007

J Cereb Blood Flow Metab

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The proinflammatory cytokine interleukin (IL)-1 mediates several forms of experimentally induced acute brain injury and has been implicated in chronic neurodegenerative disorders. The IL-1 receptor antagonist, IL-1RA, protects rodents against ischaemic brain injury, but its molecular mass (17 kDa) potentially limits the brain penetration of peripherally administered IL-1RA. We therefore sought to identify whether therapeutically effective concentrations of IL-1RA in the rat were also achieved in brain of patients with subarachnoid haemorrhage (SAH), using a peripheral administration regime that had proved to be safe and reduce peripheral inflammation in patients after stroke. An intravenous bolus of IL-1RA, followed by infusion, was administered to rats after induction of focal cerebral ischaemia. The effects of IL-1RA on brain ischaemia and the concentrations achieved in cerebrospinal fluid (CSF), were determined. Interleukin-1 receptor antagonist was similarly administered to patients with SAH, and CSF was sampled via external ventricular drains. In rats, IL-1RA significantly reduced brain injury induced by focal cerebral ischaemia. The plasma IL-1RA concentrations reached 1262 lg/mL by 30 mins, and CSF concentrations were maintained between 91 and 232 ng/mL between 1 and 24 h of infusion. In patients with SAH, IL-1RA reached a steady-state plasma concentration of 2264 lg/mL by 15 mins, and CSF concentrations were maintained at 78 to 558 ng/mL between 1 and 24 h. Intravenous delivery of IL-1RA leads to CSF concentrations in patients comparable to those that are neuroprotective in rats, and might therefore be of therapeutic benefit.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

Clark

McMahon

Gueorguieva

et al. 2007

J Cereb Blood Flow Metab

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View full text Add to dashboard Cite

show abstract

“…Expression of proinflammatory cytokines was detected in early atherogenesis, atheroma formation, and thrombosis, the last complication of atherosclerosis responsible for myocardial infarction and most strokes 4 . Moreover, these inflammatory mediators are considered to be responsible for recruiting leukocytes to the ischemic area after stroke 5 . Interleukin 1 (IL-1) is the prototypic inflammatory cytokine with widespread impact on neural function.…”

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confidence: 99%

Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke

Protti¹,

Gagliardi²,

Forte³

et al. 2013

Arq. Neuro-Psiquiatr.

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Atherosclerosis is an inflammatory disease, and ischemic stroke is one of its most common and devastating manifestations. Proinflammatory cytokines play a key role in the progression of the irreversible ischemic lesions. The presence of anti-inflammatory mediators may prevent secondary ischemic injury. Objectives: 1) To assess the relationship between stroke severity and the serum levels of IL-1β, IL-2, and IL-10; and 2) To analyze the neurological outcome after 72 h of ischemic stroke onset and expression of interleukins. Method: We measured the serum levels of IL-1β, IL-2, and IL-10 in 26 patients with acute stroke. Neurological impairment was scored using the National Institute of Health Stroke Scale within the first 72 h after stroke onset. Thirty healthy subjects were analyzed as controls. Results: Patients with IL-10 <925.0 pg/mL presented with neurological deterioration within the first 72 h. Conclusion: IL-10 may protect against ischemic injury during the acute phase of stroke.Keywords: ischemic stroke, cytokines, inflammation. RESUMOAterosclerose é considerada um doença inflamatória e o acidente vascular cerebral (AVC) isquêmico uma de suas principais manifestações. Citocinas pró-inflamatórias exercem importante função na progressão para uma lesão isquêmica irreversível. A presença de mediadores anti-inflamatórios age prevenindo a lesão isquêmica secundária. Objetivos: 1) Avaliar a relação entre gravidade do AVC e níveis de IL-1β, IL-2 e IL-10; 2) Avaliar a relação entre prognóstico neurológico nas primeiras 72 horas do AVC e o nível destas citocinas. Método: Mensuramos os níveis de IL-1β, IL-2 e IL-10 de 26 pacientes com AVC isquêmico. O comprometimento neurológico foi avaliado através da escala do National Institute of Health nas primeiras 72 horas do AVC. Trinta indivíduos saudáveis foram usados como controles. Resultados: Pacientes com IL-10 <925,0 pg/mL apresentaram deterioração neurológica nas primeiras 72 horas após o início do AVC. Conclusão: IL-10 pode apresentar um efeito protetor contra a progresso da lesão isquêmica durante a fase aguda do AVC.Palavras-chave: acidente vascular cerebral isquêmico, citocinas, inflamação.

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“…Since inflammation generates the formation of edema and can promote apoptosis, inflammatory biomarkers are potentially useful for prognosis and as prospective targets for neuroprotective therapies [9]. Although none of the cytokines that activate in the brain following stroke are CNS specific, careful investigation has confirmed that the elevation in plasma levels of these signaling molecules is owing to their production in the CNS and not from peripheral blood cells [10]. The aim of this study was to measure the serum IL-6 serially in acute ischemic stroke patients and to see the correlation of it's baseline levels with stroke severity and outcome.…”

Section: Resultsmentioning

confidence: 99%

Temporal Profile of Serum Levels of Il-6 in Acute Ischemic Stroke and Its Relationship With Stroke Severity and Outcome in Indian Population

Choudhary¹,

Chowdhury²,

Mishra³

et al. 2018

IJIMS

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Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production

Cited by 79 publications

References 43 publications

Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations

Interleukin-10 may protect against progressing injury during the acute phase of ischemic stroke

Temporal Profile of Serum Levels of Il-6 in Acute Ischemic Stroke and Its Relationship With Stroke Severity and Outcome in Indian Population

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