BACKGROUND Inflammation 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. METHODS We 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. RESULTS Decreased 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. CONCLUSION The 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.

中文翻译：

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特定的离体释放的细胞因子谱与缺血性卒中预后相关，并改善了其预测。

背景技术炎症与中风后的不良预后有关。离体细胞因子合成与中风结果之间的关系仍不清楚。我们探讨了离体细胞因子释放，循环白介素（IL）-6作为系统性炎症的标志物和中风预后之间的关联。我们评估了离体合成细胞因子在预测卒中预后中的作用。方法我们从248名缺血性中风患者中收集血液，并用脂多糖离体刺激。我们测量了合成细胞因子（TNFα，IP-10，IL-1β，IL-6，IL-8，IL-10和IL-12）和血浆IL-6的浓度。我们使用改良的兰金量表评估了卒中后3个月的功能结局。为了评估细胞因子的预后能力，我们应用了多元logistic回归，聚类分析，和多标记得分的构建。结果IP-10，TNFα，IL-1β和IL-12的释放减少；IL-10和IL-8的释放增加；血浆IL-6水平升高与预后不良有关。聚类分析确定了三组具有不同细胞因子谱的患者。结果最差的组表现出IL-10，IL-8，IL-1β和IL-6的高合成，IL-12，IP-10和TNFα的低合成，并伴有高循环IL-6水平。预后最好的组显示TNFα，IP-10，IL-12，IL-1β和IL-6的合成较高；IL-10和IL-8的合成低；和低血浆IL-6。中期结局的患者所有细胞因子的合成均较低，同时循环IL-6较低。我们构建了由离体释放的IL-12，IL-10，TNFα和血浆IL-6组成的多标记评分。将此分数添加到临床变量中导致c统计量显着增加（0.81 vs 0.73，p = 0.02）和净重分类改善。结论促炎性细胞因子的离体释放减少以及IL-10和IL-8释放增加与中风后预后不良有关。基于细胞因子的多标记评分为临床模型预测卒中预后增加了预后价值。