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The specific ex vivo released cytokine profile is associated with ischemic stroke outcome and improves its prediction

Authors
  • Klimiec-Moskal, Elzbieta1
  • Piechota, Marcin2
  • Pera, Joanna1
  • Weglarczyk, Kazimierz3
  • Slowik, Agnieszka1
  • Siedlar, Maciej3
  • Dziedzic, Tomasz1
  • 1 Jagiellonian University Medical College, ul. Botaniczna 3, Kraków, 31-503, Poland , Kraków (Poland)
  • 2 Polish Academy of Sciences, ul. Smetna 12, Krakow, 31-343, Poland , Krakow (Poland)
  • 3 Jagiellonian University Medical College, ul. Wielicka 265, Krakow, 30-663, Poland , Krakow (Poland)
Type
Published Article
Journal
Journal of Neuroinflammation
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 06, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12974-019-1691-1
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundInflammation is associated with poor outcome after stroke. A relationship between ex vivo cytokine synthesis and stroke outcome remains unclear. We explored an association between ex vivo cytokine release, circulating interleukin (IL)-6 as a marker of systemic inflammation, and stroke prognosis. We assessed the utility of ex vivo synthesized cytokines for predicting stroke outcome.MethodsWe collected blood from 248 ischemic stroke patients and stimulated it ex vivo with lipopolysaccharide. We measured concentration of synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12) and plasma IL-6. We assessed functional outcome 3 months after stroke using the modified Rankin Scale. To assess the prognostic ability of cytokines, we applied multivariate logistic regression, cluster analysis, and construction of multimarker score.ResultsDecreased release of IP-10, TNFα, IL-1β, and IL-12; increased release of IL-10 and IL-8; and higher plasma IL-6 level were associated with poor outcome. Cluster analysis identified three groups of patients with distinct cytokine profiles. The group with the worst outcome demonstrated high synthesis of IL-10, IL-8, IL-1β, and IL-6 and low synthesis of IL-12, IP-10, and TNFα accompanied by high circulating IL-6 level. The group with the best prognosis showed high synthesis of TNFα, IP-10, IL-12, IL-1β, and IL-6; low synthesis of IL-10 and IL-8; and low plasma IL-6. Patients with intermediate outcome had low synthesis of all cytokines accompanied by low circulating IL-6. We constructed a multimarker score composed of ex vivo released IL-12, IL-10, TNFα, and plasma IL-6. Addition of this score to clinical variables led to significant increase in c-statistic (0.81 vs 0.73, p = 0.02) and net reclassification improvement.ConclusionThe decreased ex vivo release of pro-inflammatory cytokines and increased release of IL-10 and IL-8 are related to poor outcome after stroke. Cytokine-based multimarker score adds prognostic value to clinical model for predicting stroke outcome.

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