Interferon-gamma to interleukin-10 ratio is negatively associated with short-term mortality risk in sepsis patients: a retrospective study based on immune balance index.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.