Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: A systematic review and meta-analysis

Bustamante, Alejandro; Sobrino, Tomás; Giralt, Dolors; García‐Berrocoso, Teresa; Llombart, Víctor; Ugarriza, Iratxe; Espadaler, Marc; Rodriguez, Noelia; Sudlow, Cathie; Castellanos, Mar; Smith, Craig J.; Rodríguez‐Yáñez, Manuel; Waje‐Andreassen, Ulrike; Tanné, David; Oto, Jun; Barber, Mark; Worthmann, Hans; Wartenberg, Katja E.; Becker, Kyra J.; Chakraborty, Baidarbhi; Oh, Seung-Hun; Whiteley, William; Castillo, José; Montaner, Joan

doi:10.1016/j.jneuroim.2014.07.015

Cited by 107 publications

(100 citation statements)

References 51 publications

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“…Furthermore, specific challenges regarding biomarkers of central nervous tissue include the penetration of BBB and the lack of correlation between functional symptoms and volume (as opposed to location) of injured tissue. According to pathophysiological processes underlying IS, potential inflammatory biomarkers may be classified as released by: (i) astroglial activation and neuronal injury (Table 1) [146,147,148,149,150,151,152,153,154,155,156,157]; (ii) systemic inflammatory response (Table 2) [158,159,160,161,162,163,164,165,166,167,168,169,170,171,172,173,174,175,176,177,178,179]; (iii) dysfunctional endothelium (Table 3) [180,181,182,183,184,185,186] (Figure 4). …”

Section: Inflammatory Mediators As Potential Diagnostic or Prognosmentioning

confidence: 99%

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

Bonaventura

Liberale

Vecchiè

et al. 2016

IJMS

125

104

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After an acute ischemic stroke (AIS), inflammatory processes are able to concomitantly induce both beneficial and detrimental effects. In this narrative review, we updated evidence on the inflammatory pathways and mediators that are investigated as promising therapeutic targets. We searched for papers on PubMed and MEDLINE up to August 2016. The terms searched alone or in combination were: ischemic stroke, inflammation, oxidative stress, ischemia reperfusion, innate immunity, adaptive immunity, autoimmunity. Inflammation in AIS is characterized by a storm of cytokines, chemokines, and Damage-Associated Molecular Patterns (DAMPs) released by several cells contributing to exacerbate the tissue injury both in the acute and reparative phases. Interestingly, many biomarkers have been studied, but none of these reflected the complexity of systemic immune response. Reperfusion therapies showed a good efficacy in the recovery after an AIS. New therapies appear promising both in pre-clinical and clinical studies, but still need more detailed studies to be translated in the ordinary clinical practice. In spite of clinical progresses, no beneficial long-term interventions targeting inflammation are currently available. Our knowledge about cells, biomarkers, and inflammatory markers is growing and is hoped to better evaluate the impact of new treatments, such as monoclonal antibodies and cell-based therapies.

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Section: Inflammatory Mediators As Potential Diagnostic or Prognosmentioning

confidence: 99%

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

Bonaventura

Liberale

Vecchiè

et al. 2016

IJMS

125

104

View full text Add to dashboard Cite

show abstract

“…Variability in biomarker measurement, particularly between sites, has been identified. For example, in a meta-analysis of IL-6 in stroke and another meta-analysis of BNP in ischemic stroke, >1000 fold difference in mean protein concentration was observed between sites 40, 41 . Reducing such variability will be essential to replicate promising biomarkers and biomarker panels in stroke.…”

Section: Molecules To Include In Biomarker Panels and Their Measurementmentioning

confidence: 99%

Biomarker Panels in Ischemic Stroke

Jickling¹,

Sharp²

2015

Stroke

110

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“…2 The endogenous IL-1 receptor antagonist (IL-1Ra) blocks all known actions of IL-1 by competitively inhibiting the IL-1 receptor 1, without any reported agonist activity. 3 IL-1Ra markedly attenuates experimental brain injury in experimental cerebral ischemia, showing efficacy in aged and comorbid animals, when administered peripherally by subcutaneous (SC) or intravenous (IV) routes, and with delayed administration.…”

Section: Introductionmentioning

confidence: 99%

SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke)

Smith

Hulme

Vail

et al. 2018

Stroke

Self Cite

144

109

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F o r S t r o k Background and PurposeThe pro-inflammatory cytokine interleukin-1 (IL-1) has a deleterious role in cerebral ischemia, which is attenuated by IL-1 receptor antagonist (IL-1Ra). IL-1 induces peripheral inflammatory mediators, such as interleukin-6 (IL-6), which are associated with worse prognosis after ischemic stroke. We investigated whether subcutaneous (SC) IL-1Ra reduces the peripheral inflammatory response in acute ischemic stroke. MethodsSCIL-STROKE was a single-center, double-blind, randomized, placebo-controlled phase 2 trial of SC IL-1Ra (100mg administered twice daily for three days) in patients presenting within 5h of ischemic stroke onset. Randomization was stratified for baseline NIHSS score and thrombolysis. Measurement of plasma IL-6 and other peripheral inflammatory markers was undertaken at five time points. The primary outcome was difference in concentration of log(IL-6) as area under the curve to Day 3. Secondary outcomes included exploratory effect of IL-1Ra on three month outcome with the modified Rankin Scale (mRS). ResultsWe recruited 80 patients (mean age 72, median NIHSS 12) of whom 73% received intravenous thrombolysis with alteplase. IL-1Ra significantly reduced plasma and plasma C-reactive protein (p<0.001). IL-1Ra was well-tolerated with no safety concerns.Allocation to IL-1Ra was not associated with a favorable outcome on mRS: OR (95% CI) = 0.67 (0.29 to 1.52); p=0.34. Exploratory mediation analysis suggested that IL-1Ra improved clinical outcome by reducing inflammation, but there was a statistically significant, alternative mechanism countering this benefit. ConclusionsIL-1Ra reduced plasma inflammatory markers which are known to be associated with worse clinical outcome in ischemic stroke. SC IL-1Ra is safe and well-tolerated. Further 3

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Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: A systematic review and meta-analysis

Cited by 107 publications

References 51 publications

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

Update on Inflammatory Biomarkers and Treatments in Ischemic Stroke

Biomarker Panels in Ischemic Stroke

SCIL-STROKE (Subcutaneous Interleukin-1 Receptor Antagonist in Ischemic Stroke)

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