Kuhle J, Lindberg R L P, Regeniter A, Mehling M, Steck A J, Kappos L, Czaplinski A
Department of Neurology, University Hospital Basel, Basel, Switzerland.
Eur J Neurol. 2009 Jun;16(6):771-4. doi: 10.1111/j.1468-1331.2009.02560.x. Epub 2009 Feb 19.
Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.
We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.
MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum (P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis (r = -0.407; P = 0.075).
We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.
肌萎缩侧索硬化症(ALS)传统上被认为是一种神经退行性疾病。在ALS患者的中枢神经系统组织中已观察到炎症反应。我们研究了促炎趋化因子在ALS中的表达及其预后相关性。
我们分析了20例ALS患者和20例非炎性神经疾病(NIND)患者血清和脑脊液(CSF)中的9种趋化因子,即嗜酸性粒细胞趋化因子、嗜酸性粒细胞趋化因子-3、白细胞介素-8(IL-8)、干扰素诱导蛋白10(IP-10)、单核细胞趋化蛋白-1(MCP-1)、单核细胞趋化蛋白-4、巨噬细胞衍生趋化因子(MDC)、巨噬细胞炎性蛋白-1β(MIP-1β)以及血清胸腺和活化调节趋化因子(TARC)。
ALS患者脑脊液中MCP-1和IL-8水平显著高于NIND患者(分别为1304 pg/ml对1055 pg/ml,P = 0.013;22.7 pg/ml对18.6 pg/ml,P = 0.035)。脑脊液中MCP-1和IL-8的表达高于血清(P < 0.001)。首发症状至诊断时间较短的ALS患者脑脊液中MCP-1水平有升高趋势(r = -0.407;P = 0.075)。
我们证实了之前关于ALS患者脑脊液中MCP-1水平升高的研究结果。此外,脑脊液中IL-8水平升高提示小胶质细胞活化后促炎细胞因子级联反应受到刺激。我们发现诊断延迟较短的患者MCP-1值有升高趋势,而这些患者生存期也较短。这可能表明较高的MCP-1水平与疾病快速进展有关。