Maxeiner Horst-Guenter, Marion Schneider E, Kurfiss Sina-Tatjana, Brettschneider Johannes, Tumani Hayrettin, Bechter Karl
Clinic for Psychiatry and Psychotherapy II, Ulm University, BKH-Guenzburg, Germany.
Department of Neurology, RKU Ulm University, Germany.
Cytokine. 2014 Sep;69(1):62-7. doi: 10.1016/j.cyto.2014.05.008. Epub 2014 Jun 7.
The present study aimed at profiling inflammatory cytokines for neurological and psychiatric diseases. A total of 86 patients with meningitis, multiple sclerosis, tension-type headache, idiopathic facial nerve palsy (IFNP), affective and schizophrenic disorders were tested for both, serum and cerebrospinal fluid (CSF) using a multiplexed cytokine ELISA for IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-8/CXCL8, IL-10, IL12p70, IL-13 and IL-17. Cases with viral and bacterial meningitis had unequivocally higher cytokine concentrations in the CSF when compared with serum. Bacterial meningitis was unique by extremely elevated IL-17, TNF-α and IL-1β, indicating a plethora of inflammatory pathways, selectively activated in the CSF. In relapsing multiple sclerosis, IFN-γ and IL-10 were elevated in both, serum and CSF, but IL-12p70, IL-5, IL-13, and TNF-α were more prominent in serum than in CSF. Qualitatively similar biomarker patterns were detected in patients with idiopathic facial nerve palsy and tension-type cephalgia. Affective and schizophrenic disorders clearly present with an inflammatory phenotype in the CSF and also serum, the cytokines determined were in general higher in schizophrenia. Except IFN-γ, schizophrenic patients had higher IL-12p70 and a trend of higher IL-10 and IL-13 in serum suggesting a more prominent TH2-type counter regulatory immune response than in affective disorders. These differences were also mirrored in the CSF. Elevated IL-8 appears to be the most sensitive marker for inflammation in the CSF of all diseases studied, whereas TNF-α was restricted to peripheral blood. With the exception of IL-8, all but viral and bacterial meningitis, studied, displayed higher means of elevated lymphokine concentrations in the serum than in the CSF. This observation supports the concept of immunological crosstalk between periphery and intrathecal immunity in neurological and psychiatric diseases.
本研究旨在分析神经和精神疾病的炎性细胞因子。使用多重细胞因子酶联免疫吸附测定法检测了86例患有脑膜炎、多发性硬化症、紧张型头痛、特发性面神经麻痹（IFNP）、情感障碍和精神分裂症的患者的血清和脑脊液（CSF）中的干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、白细胞介素-5（IL-5）、白细胞介素-8/趋化因子配体8（IL-8/CXCL8）、白细胞介素-10（IL-10）、白细胞介素12p70、白细胞介素-13（IL-13）和白细胞介素-17。与血清相比，病毒性和细菌性脑膜炎患者脑脊液中的细胞因子浓度明显更高。细菌性脑膜炎的独特之处在于白细胞介素-17、肿瘤坏死因子-α和白细胞介素-1β极度升高，表明脑脊液中选择性激活了大量炎症途径。在复发型多发性硬化症中，血清和脑脊液中的干扰素-γ和白细胞介素-10均升高，但白细胞介素12p70、白细胞介素-5、白细胞介素-13和肿瘤坏死因子-α在血清中的含量比脑脊液中更显著。在特发性面神经麻痹和紧张型头痛患者中检测到了定性相似的生物标志物模式。情感障碍和精神分裂症在脑脊液和血清中均明显呈现出炎症表型，精神分裂症患者中所检测的细胞因子总体上更高。除干扰素-γ外，精神分裂症患者血清中的白细胞介素12p70更高，白细胞介素-10和白细胞介素-13有升高趋势，这表明与情感障碍相比，其TH2型反调节免疫反应更突出。这些差异在脑脊液中也有体现。在所研究的所有疾病中，脑脊液中白细胞介素-8升高似乎是炎症最敏感的标志物，而肿瘤坏死因子-α仅在外周血中升高。除白细胞介素-8外，除病毒性和细菌性脑膜炎外，所研究的其他疾病血清中升高的淋巴因子浓度均值均高于脑脊液。这一观察结果支持了神经和精神疾病中外周免疫与鞘内免疫之间存在免疫串扰的概念。
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