Departments of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
Stroke. 2012 Sep;43(9):2300-6. doi: 10.1161/STROKEAHA.112.657411. Epub 2012 Jul 12.
Fractalkine (CX3CL1) is a unique chemokine that is constitutively expressed on neurons where it serves as an adhesion molecule for lymphocytes and monocytes. CX3CL1 may also be cleaved from the surface of these cells and enter the circulation to act as a traditional chemokine. CX3CL1 could thus influence the inflammatory response after stroke. We hypothesized that patients with higher plasma CX3CL1 after stroke would have a more robust inflammatory response and experience worse outcome.
Plasma CX3CL1 concentrations were assessed in 85 patients who were part of a larger study evaluating immune responses after ischemic stroke; CX3CL1 values were available from Day 1 to Day 180 after stroke onset. CX3CL1 was correlated to measures of inflammation and its effect on outcome assessed.
At 1 day after stroke, CX3CL1 was lower in patients with severe strokes. At 180 days after stroke, CX3CL1 concentrations were lower in patients with poor outcome. The association of CX3CL1 and outcome at 180 days was independent of initial stroke severity. Plasma CX3CL1 at 180 days was inversely associated with systemic markers of inflammation, including white blood cell counts and high-sensitivity C-reactive protein.
In contrast to our original hypothesis, lower concentrations of CX3CL1 are associated with worse stroke outcome. In light of recent studies suggesting an immunomodulatory and neuroprotective role for CX3CL1 in a variety of neurodegenerative diseases, a therapeutic role for CX3CL1 in stroke recovery should be considered.
趋化因子(CX3CL1)是一种独特的趋化因子,在神经元上持续表达,作为淋巴细胞和单核细胞的黏附分子。CX3CL1 也可能从这些细胞表面被切割下来并进入循环,作为一种传统的趋化因子发挥作用。因此,CX3CL1 可能会影响中风后的炎症反应。我们假设中风后血浆 CX3CL1 水平较高的患者会有更强烈的炎症反应,并经历更差的结局。
85 名参与评估缺血性中风后免疫反应的更大研究的患者的血浆 CX3CL1 浓度进行了评估;中风发作后第 1 天至第 180 天可获得 CX3CL1 值。对 CX3CL1 与炎症指标的相关性及其对结局的影响进行了评估。
中风后第 1 天,严重中风患者的 CX3CL1 水平较低。中风后第 180 天,预后不良的患者 CX3CL1 浓度较低。180 天后 CX3CL1 与结局的相关性独立于初始中风严重程度。180 天时的血浆 CX3CL1 与全身炎症标志物呈负相关,包括白细胞计数和高敏 C 反应蛋白。
与我们最初的假设相反,较低浓度的 CX3CL1 与更差的中风结局相关。鉴于最近的研究表明 CX3CL1 在多种神经退行性疾病中具有免疫调节和神经保护作用,应考虑 CX3CL1 在中风恢复中的治疗作用。