School of Clinical medicine of Weifang Medical College, Weifang, China.
The Department of Neurology, Affiliated Hospital of Weifang Medical College, Weifang, China.
J Neuroimmunol. 2018 Jul 15;320:58-63. doi: 10.1016/j.jneuroim.2018.04.003. Epub 2018 Apr 10.
Macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory responses, has been reported to link to the pathophysiology of cardiovascular disease and depression. The aim of this study was to test the possible association between plasma MIF and the development of post-stroke depression (PSD) in Chinese patients with acute ischemic stroke (AIS).
The first-ever AIS patients who were hospitalized at Affiliated Hospital of Weifang Medical College during the period from November 2015 to September 2017 were included. Neurological and neuropsychological evaluations were conducted at the 3-month follow-up. Plasma concentrations of MIF were tested by Quantikine Human MIF Immunoassay. Plasma levels of homocysteine (HCY), C-reactive protein (CRP) and Interleukin 6 (IL-6) were also tested. Results were expressed as percentages for categorical variables and as medians (Interquartile range-IQR) for the continuous variables.
Finally, 333 stroke patients were included, and 95 out of those patients (28.5%) were classified as major depression. In the patients with major depression, plasma levels of MIF were higher compared with those in patients free-depression [27.3(IQR, 23.5-34.9) ng/ml vs. 20.9(IQR, 17.0-24.8) ng/ml; Z = 8.369, P < 0.001]. For each 1unit increase of MIF, the unadjusted and adjusted risk of PSD increased by 18% (odds ratios [OR]: 1.18; 95% confidence interval [CI], 1.13-1.23, P < 0.001) and 11% (1.11; 1.02-1.16, P = 0.001), respectively. In a multivariate model using the elevated levels of MIF (≥median) vs. normal (<median) together with the other significant clinical variables, the marker displayed prognostic information (PSD: OR for fourth quartile, 3.05 [95% CI, 1.65-6.11; P < 0.001]). When MIF was added to the model containing established significant risk factors, Area Under the Receiver Operating Characteristic curve (AUROC; standard error) was increased from 0.81(0.025) to 0.86(0.019). A significant difference in the AUROC between the established risk factors alone and the addition of MIF was observed (difference, 0.05[0.006]; P = 0.004).
The present study demonstrated that elevated plasma levels of MIF at admission were associated with increased risk of PSD in the next three months and might be useful in identifying stroke at risk for PSD for early prevention strategies.
巨噬细胞移动抑制因子（MIF）是先天免疫和炎症反应的核心细胞因子，据报道与心血管疾病和抑郁症的病理生理学有关。本研究旨在检测中国急性缺血性脑卒中（AIS）患者血浆 MIF 与卒中后抑郁（PSD）发展之间的可能关联。
纳入 2015 年 11 月至 2017 年 9 月期间在潍坊医学院附属医院首次住院的 AIS 患者。在 3 个月随访时进行神经和神经心理学评估。通过 Quantikine 人 MIF 免疫测定法检测血浆 MIF 浓度。还检测了血浆同型半胱氨酸（HCY）、C 反应蛋白（CRP）和白细胞介素 6（IL-6）的水平。分类变量的结果表示为百分比，连续变量的结果表示为中位数（四分位距-IQR）。
最终纳入 333 例脑卒中患者，其中 95 例（28.5%）患者患有重度抑郁症。在患有重度抑郁症的患者中，血浆 MIF 水平高于无抑郁患者[27.3（IQR，23.5-34.9）ng/ml 比 20.9（IQR，17.0-24.8）ng/ml；Z=8.369，P<0.001]。对于 MIF 的每增加 1 单位，未调整和调整后的 PSD 风险分别增加 18%（优势比[OR]：1.18；95%置信区间[CI]，1.13-1.23，P<0.001）和 11%（1.11；1.02-1.16，P=0.001）。在使用升高的 MIF 水平（≥中位数）与其他显著临床变量的多元模型中，该标志物显示出预后信息（PSD：四分位距第四的 OR，3.05[95%CI，1.65-6.11；P<0.001]）。当 MIF 被添加到包含已建立的显著危险因素的模型中时，接收器操作特征曲线（AUROC；标准误差）下的面积从 0.81（0.025）增加到 0.86（0.019）。仅使用已建立的危险因素和添加 MIF 的 AUROC 之间存在显著差异（差异，0.05[0.006]；P=0.004）。
本研究表明，入院时升高的血浆 MIF 水平与接下来三个月 PSD 的风险增加相关，可能有助于识别有 PSD 风险的脑卒中患者，以便进行早期预防策略。
