干扰素γ与白细胞介素-10的比值与败血症患者的短期死亡风险呈负相关：一项基于免疫平衡指数的回顾性研究

摘要(中文译文)

脓毒症是由宿主对感染反应失调所致的危及生命的器官功能障碍。其免疫病理特征表现为促炎与抗炎反应之间的动态失衡。干扰素-γ（IFN-γ）和白细胞介素-10（IL-10）分别是促炎和抗炎介质的代表性因子，二者比值（IIR）可能更敏感地反映脓毒症患者的免疫平衡状态。然而，既往研究多聚焦于单一细胞因子的预后价值，IIR与短期死亡风险之间的关联及其预测效能尚不明确。我们回顾性分析了2023年12月至2026年1月期间广西医科大学第二附属医院重症监护病房（ICU）收治的411例脓毒症患者的临床数据。根据ICU入住后24小时内首次测定的IIR值三分位数将患者分为低、中、高IIR组。采用Kaplan-Meier曲线及log-rank检验比较各组生存情况。采用多因素Cox比例风险回归模型评估IIR与死亡风险之间的关联。进行限制性立方样条分析以探讨潜在的剂量-反应关系，随后进行阈值效应分析。构建受试者工作特征曲线以评估IIR的预测价值，并进行亚组分析以检验结果的稳健性。共纳入411例患者。Kaplan-Meier分析显示，IIR水平较高的患者14天和28天全因死亡风险显著降低（log-rank P < 0.001）。校正混杂因素后，多因素Cox回归证实高IIR水平与14天死亡率（HR = 0.48，95% CI：0.30-0.77，P < 0.05）和28天死亡率（HR = 0.62，95% CI：0.42-0.90，P < 0.05）均呈独立负相关。限制性立方样条分析揭示了IIR与短期死亡率之间的非线性关联。两段式Cox回归确定14天死亡率的拐点为0.066，28天死亡率的拐点为0.073。受试者工作特征曲线分析表明，IIR对脓毒症患者短期死亡率具有良好的预测价值。亚组分析结果一致， predefined亚组间未观察到显著交互作用。IFN-γ/IL-10比值与脓毒症患者14天和28天死亡风险呈非线性负相关。较高的IIR水平与短期死亡率降低显著相关，提示该免疫平衡指标可作为短期预后的独立预测因子。

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Its immunopathology is characterized by a dynamic imbalance between pro-inflammatory and anti-inflammatory responses. Interferon-γ (IFN-γ) and interleukin-10 (IL-10) are representative pro- and anti-inflammatory mediators, respectively, and their ratio (IIR) may provide a more sensitive reflection of immune balance in patients with sepsis. However, most previous studies have focused on the prognostic value of individual cytokines, and the association between IIR and short-term mortality risk, as well as its predictive performance, remains unclear. We retrospectively analyzed clinical data from 411 patients with sepsis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Guangxi Medical University between December 2023 and January 2026. Patients were divided into low, intermediate, and high IIR groups according to tertiles of the first IIR value measured within 24 h after ICU admission. Kaplan-Meier curves were generated to compare survival across groups using the log-rank test. Multivariable Cox proportional hazards regression models were used to evaluate the association between IIR and mortality risk. Restricted cubic spline analysis was performed to explore potential dose-response relationships, followed by threshold effect analysis. Receiver operating characteristic curves were constructed to assess the predictive value of IIR, and subgroup analyses were conducted to examine the robustness of the findings. A total of 411 patients were included. Kaplan-Meier analysis showed that patients with higher IIR levels had significantly lower risks of 14-day and 28-day all-cause mortality (log-rank P < 0.001). After adjustment for confounders, multivariable Cox regression confirmed an independent negative association between high IIR levels and both 14-day mortality (HR = 0.48, 95% CI: 0.30-0.77, P < 0.05) and 28-day mortality (HR = 0.62, 95% CI: 0.42-0.90, P < 0.05). Restricted cubic spline analysis revealed a nonlinear association between IIR and short-term mortality. Two-piecewise Cox regression identified inflection points at 0.066 for 14-day mortality and 0.073 for 28-day mortality. Receiver operating characteristic curve analysis indicated that IIR had favorable predictive value for short-term mortality in patients with sepsis. Subgroup analyses yielded consistent associations, with no significant interaction observed across predefined subgroups. The IFN-γ/IL-10 ratio was nonlinearly and negatively associated with 14-day and 28-day mortality risk in patients with sepsis. Higher IIR levels were significantly associated with reduced short-term mortality, suggesting that this immune balance index may serve as an independent predictor of short-term prognosis.

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