Zidovec-Lepej Snjezana, Vilibic-Cavlek Tatjana, Ilic Maja, Gorenec Lana, Grgic Ivana, Bogdanic Maja, Radmanic Leona, Ferenc Thomas, Sabadi Dario, Savic Vladimir, Hruskar Zeljka, Svitek Luka, Stevanovic Vladimir, Peric Ljiljana, Lisnjic Dubravka, Lakoseljac Danijela, Roncevic Dobrica, Barbic Ljubo
Department of Immunological and Molecular Diagnostics, University Hospital for Infectious Diseases "Dr Fran Mihaljevic", 10000 Zagreb, Croatia.
Department of Virology, Croatian Institute of Public Health,10000 Zagreb, Croatia.
Vaccines (Basel). 2022 Oct 29;10(11):1825. doi: 10.3390/vaccines10111825.
Tick-borne encephalitis virus (TBEV) is one of the most significant arboviruses affecting the human central nervous system (CNS) in Europe. Data on cytokine response in TBEV infection are limited.
We analyzed the cytokine response in serum, cerebrospinal fluid (CSF) and urine samples of patients with TBE. The control group consisted of patients with 'febrile headache' who had normal CSF cytology. The panel included 12 cytokines: TNF-α, IL-6, Th1 (IL-2, IFN-γ), Th2 (IL-4, IL-5, IL-13), Th9 (IL-9), Th17 (IL-17A, IL-17F), Th22 (IL-22) cytokines and IL-10.
TBE patients were more likely to have increased levels of IL-6 and IFN-γ in CSF compared to controls (85.7% vs. 58.8% and 85.7% vs. 47.1%, respectively). However, concentrations of IL-6 (the most abundant cytokine in the CSF of both groups), IL-10 and IL-9 were lower in TBEV patients compared with controls, but the difference was statistically significant for IL-9 only ( = 0.001). By analyzing the cytokine levels in different clinical samples, all measured cytokines were detected in the serum, with the highest concentrations found for IFN-γ, TNF-α, IL-10, IL-17F and IL-22. Higher concentrations of cytokines in the CSF compared with serum were observed for IL-5, IL-6 and IL-22. All cytokines except IL-13 were detectable in urine but in a small proportion of patients, except for IL-22, which was detectable in 95.8% of patients.
Cytokine composition in different clinical samples of TBE patients reveals a different network of early innate immune response cytokines, Th1, Th2, Th9, Th22, Th17 and anti-inflammatory cytokines.
蜱传脑炎病毒（TBEV）是欧洲影响人类中枢神经系统（CNS）的最重要虫媒病毒之一。关于TBEV感染中细胞因子反应的数据有限。
我们分析了蜱传脑炎（TBE）患者血清、脑脊液（CSF）和尿液样本中的细胞因子反应。对照组由脑脊液细胞学检查正常的“发热性头痛”患者组成。检测的细胞因子包括12种：肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、辅助性T细胞1（Th1）（白细胞介素-2、干扰素-γ）、辅助性T细胞2（Th2）（白细胞介素-4、白细胞介素-5、白细胞介素-13）、辅助性T细胞9（Th9）（白细胞介素-9）、辅助性T细胞17（Th17）（白细胞介素-17A、白细胞介素-17F）、辅助性T细胞22（Th22）（白细胞介素-22）细胞因子和白细胞介素-10。
与对照组相比，TBE患者脑脊液中IL-6和干扰素-γ水平升高的可能性更大（分别为85.7%对58.8%和85.7%对47.1%）。然而，TBEV患者脑脊液中IL-6（两组脑脊液中含量最丰富的细胞因子）、IL-10和IL-9的浓度低于对照组，但仅IL-9的差异具有统计学意义（P = 0.001）。通过分析不同临床样本中的细胞因子水平，所有检测的细胞因子在血清中均有检出，其中干扰素-γ、TNF-α、IL-10、IL-17F和IL-22的浓度最高。与血清相比，脑脊液中IL-5、IL-6和IL-22的细胞因子浓度更高。除IL-13外，所有细胞因子在尿液中均可检出，但检出患者比例较小，IL-22除外，95.8%的患者尿液中可检测到IL-22。
TBE患者不同临床样本中的细胞因子组成揭示了早期先天性免疫反应细胞因子、Th1、Th2、Th9、Th22、Th17和抗炎细胞因子的不同网络。
