Wen Yanhan, Tong Yeqing, Gong Lei, Li Aqian, Huang Xiaoxia, Tian Tingting, Liu Tiezhu, Sun Lina, Li Jiandong, Li Dexin, Liang Mifang, Wu Wei, Wu Jiabing, Wang Shiwen
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Department of Infectious Diseases, Hubei Provincial Center for Disease Control and Prevention, Wuhan 430070, China.
Biosaf Health. 2025 Mar 26;7(2):83-93. doi: 10.1016/j.bsheal.2025.03.005. eCollection 2025 Apr.
Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening tick-borne disease characterized by cytokine dysregulation and immune-mediated hyperinflammation. This multicenter retrospective study analyzed the dynamics of 17 cytokines across acute and recovery phases using 287 serum samples collected between 2010 and 2023 from high-incidence regions of China, evaluating their associations with disease severity, sex, age, and antibody responses. The results demonstrated that elevations of interleukin (IL)-6, interferon (IFN)-α, IL-8, and IFN-γ-induced protein 10 (IP-10) during the acute phase were associated with hyperinflammation, while IL-10 balanced inflammatory control and may have contributed to viral persistence. During recovery, most cytokines declined; however, IL-8 and IP-10 remained elevated longer in some patients, reflecting heterogeneity in recovery trajectories. Severe cases exhibited significantly higher levels of IL-10, IFN-γ, IL-6, IFN-α, tumor necrosis factor (TNF)-α, IL-8, and IP-10, underscoring their potential as biomarkers for disease severity prediction. Sex-based differences revealed higher IFN-γ and IL-8 levels in females, potentially due to hormonal and genetic factors, while older patients exhibited elevated IL-10, IFN-γ, and IFN-α, reflecting immune dysregulation and age-related shifts in adaptive immunity. Correlation analysis revealed distinct immune response patterns, with IL-10 strongly correlating with IFN-γ and minimal antibody-cytokine associations observed during the acute phase. In contrast, in the recovery phase, immunoglobulin G (IgG) negatively correlated with IL-10, IFN-γ, and IP-10, and immunoglobulin M (IgM) positively correlated with IL-10, IFN-γ, IL-6, IFN-α, TNF-α, IL-8, and IP-10, reflecting dynamic immune regulation and the interplay between humoral and cellular immunity. These findings provide critical insights into the immunopathogenesis of SFTS, supporting the development of cytokine-targeted therapies and advanced diagnostic tools to improve clinical outcomes.
严重发热伴血小板减少综合征（SFTS）是一种危及生命的蜱传疾病，其特征为细胞因子失调和免疫介导的过度炎症反应。这项多中心回顾性研究使用2010年至2023年间从中国高发病区收集的287份血清样本，分析了17种细胞因子在急性期和恢复期的动态变化，评估它们与疾病严重程度、性别、年龄及抗体反应的关联。结果表明，急性期白细胞介素（IL）-6、干扰素（IFN）-α、IL-8和IFN-γ诱导蛋白10（IP-10）升高与过度炎症反应相关，而IL-10平衡炎症控制并可能促成病毒持续存在。在恢复期，大多数细胞因子水平下降；然而，部分患者的IL-8和IP-10升高时间更长，反映出恢复轨迹的异质性。重症病例中IL-10、IFN-γ、IL-6、IFN-α、肿瘤坏死因子（TNF）-α、IL-8和IP-10水平显著更高，突出了它们作为疾病严重程度预测生物标志物的潜力。基于性别的差异显示，女性的IFN-γ和IL-8水平较高，可能是由于激素和遗传因素，而老年患者的IL-10、IFN-γ和IFN-α水平升高，反映出免疫失调以及适应性免疫中与年龄相关的变化。相关性分析揭示了不同的免疫反应模式，急性期IL-10与IFN-γ强烈相关，且观察到抗体与细胞因子之间的关联极小。相反，在恢复期，免疫球蛋白G（IgG）与IL-10、IFN-γ和IP-10呈负相关，免疫球蛋白M（IgM）与IL-10、IFN-γ、IL-6、IFN-α、TNF-α、IL-8和IP-10呈正相关，反映了动态免疫调节以及体液免疫与细胞免疫之间的相互作用。这些发现为SFTS的免疫发病机制提供了关键见解，支持开发针对细胞因子的疗法和先进诊断工具以改善临床结局。
