Mei Feng-Jun, Ishizu Takaaki, Murai Hiroyuki, Osoegawa Manabu, Minohara Motozumi, Zhang Kun-Nan, Kira Jun-ichi
Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Neurol Sci. 2005 Jan 15;228(1):75-85. doi: 10.1016/j.jns.2004.10.001. Epub 2004 Nov 12.
To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.
为研究慢性炎性脱髓鞘性多发性神经病（CIDP）和血管炎性神经病（VN）患者脑脊液（CSF）中多种细胞因子和趋化因子的细胞内及细胞外水平，采用基于荧光微球的多重免疫分析法检测了14例CIDP患者、8例VN患者及25例其他非炎性神经系统疾病（OND）患者CSF上清液中16种细胞因子，即白细胞介素-1β（IL-1β）、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12（p70）、IL-13、IL-17、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、粒细胞集落刺激因子（G-CSF）、单核细胞趋化蛋白-1（MCP-1）和巨噬细胞炎性蛋白-1β（MIP-1β），并同时通过流式细胞术检测CSF中CD4⁺T细胞内IFN-γ和IL-4的产生情况。在CSF上清液中，与OND相比，预处理后的CIDP患者IL-17、IL-8和IL-6水平显著升高，IL-4、IL-5和IL-7水平显著降低。预处理后的VN患者IL-6、IL-8和IL-10水平显著升高。在CIDP中，IL-17和IL-8水平均与CSF蛋白水平密切相关，尽管IL-6水平的相关性较弱。在CSF CD4⁺T细胞中，与OND相比，CIDP患者IFN-γ⁺IL-4⁻细胞百分比显著升高，但VN患者无此现象，即使在CSF无细胞增多的情况下，CIDP患者细胞内IFN-γ/IL-4比值仍显著升高。静脉注射免疫球蛋白（IVIG）治疗无反应者CSF中IFN-γ⁻IL-4⁺CD4⁺T细胞百分比显著降低，且细胞内IFN-γ/IL-4比值往往高于有反应者。Th1细胞因子IL-17的显著上调和Th2细胞因子的下调，以及产生IFN-γ的CD4⁺T细胞浸润是CIDP的有用标志物，而在VN患者的CSF中几种Th2细胞因子上调。
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