ABSTRACT

Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study.

Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships.

Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3–6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82–9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes.

Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions.

摘要

目的：虽然粒细胞集落刺激因子 (G-CSF) 在实验性缺血性卒中 (IS) 中显示出有益作用，但这些作用尚未在临床上重现。中小型观察性研究报告了 G-CSF 与中风严重程度和中风后功能结果的不同关联，促使他们在更大的研究中进行调查。

方法：在急性期和 3 个月后对来自 Sahlgrenska Academy 缺血性中风研究的 IS 患者（N = 435；36% 女性；平均年龄 57 岁）测量内源性血清 G-CSF (S-GCSF)。萨尔西斯）。根据美国国立卫生研究院卒中量表 (NIHSS) 对卒中严重程度进行评分，改良 Rankin 量表 (mRS) 评估卒中后 3 个月和 2 年的功能结果。具有混杂因素调整的相关性和逻辑回归分析评估了这些关系。

结果：急性 S-GCSF 水平比卒中后 3 个月时高 23%（p < 0.001）。急性 G-CSF 与中风严重程度五分位数（r = 0.12，p = 0.013）和高敏 C 反应蛋白（r = 0.29，p < 0.001）呈弱相关。S-GCSF（作为五分位数，q）与 3 个月时的不良功能结果之间的关联（mRS 3-6；S-GCSF-q5 与 S-GCSF-q1，年龄和性别调整的优势比：4.27, 95 % 置信区间：1.82–9.99；p = 0.001）经受住了对心血管危险因素和卒中亚型的调整，但未对卒中严重程度进行额外校正。S-GSCF 和绝对 3 个月 S-GCSF 的卒中后变化与 3 个月或 2 年的功能结果无关。

讨论：严重 IS 患者卒中后早期 S-GCSF 增加，并与 3 个月的不良功能结果相关。S-GCSF 和 3 个月 S-GCSF 的变化似乎不太重要，S-GCSF 可能反映了大面积梗塞的炎症。