Longitudinal analysis of cytokine dynamics in severe fever with thrombocytopenia syndrome patients — High-incidence regions of China (2010–2023)

Abstract

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.