Intraoperative Cytokines and Postcraniotomy Infection in Benign Brain Tumors: An Exploratory Prospective Study

Objective: Intracranial infection is a severe complication that can occur following neurosurgery, and early diagnosis is crucial for improving patient prognosis. In this study, we aimed to investigate, from an exploratory perspective, whether the immune microenvironment of intraoperative cerebrospinal fluid (CSF) is associated with postoperative intracranial infection (PII) in patients undergoing craniotomy for benign brain tumors. Methods: A total of 134 patients undergoing neurosurgery for benign brain tumors were included and categorized into an infection group (n = 18) and a non-infection group (n = 116). CSF samples were collected aseptically immediately after dural opening during surgery. The concentrations of 16 cytokines, including monocyte chemoattractant protein-1 (MCP-1); macrophage inflammatory protein-1α (MIP-1α) and MIP-1β; interleukin (IL)-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17; interferon (IFN)-α and IFN-γ; tumor necrosis factor-α (TNF-α); and granulocyte colony-stimulating factor (G-CSF), were quantified using Cytometric Bead Array (CBA) technology. An independent samples t-test was used for normally distributed data, while the Mann-Whitney U test was applied for non-normally distributed data. Group comparisons were performed using independent-samples t-tests or Mann-Whitney U tests for continuous variables and χ² tests or Fisher's exact tests for categorical variables. The Benjamini-Hochberg false discovery rate (FDR) correction was applied to all 16 cytokines to control for multiple testing. Receiver operating characteristic (ROC) curve analysis was performed to assess discriminatory capacity. Statistical significance was defined as p < 0.05. Results: PII developed in 18 of 134 patients (13.4%). Age (47.78 vs. 54.86, p = 0.028) and operative duration (390 vs. 244 min, p = 0.005) showed differences in unadjusted analyses. In the unadjusted comparisons, MCP-1 and IL-4 levels were found to be significantly lower in the infection group (MCP-1: 57.78 vs. 116.03 pg/mL, p = 0.003; IL-4: 24.38 vs. 28.18 pg/mL, p = 0.032). No cytokine remained significant after FDR correction. The ROC analysis showed that age and IL-4 demonstrated mild discriminatory performance, with AUC values of 0.665 (95% CI 0.526-0.803, p = 0.025) and 0.657 (95% CI 0.540-0.774, p = 0.032), while MCP-1 and operative duration demonstrated modest discriminatory performance, with AUC values of 0.716 (95% CI 0.595-0.838, p = 0.003) and 0.708 (95% CI 0.578-0.838, p = 0.002). Conclusions: In this study, single-point intraoperative CSF cytokines were not significantly associated with PII after stringent correction for multiple testing, and did not provide a validated clinical prediction tool. The unadjusted and direction-corrected findings for MCP-1 and IL-4 remain exploratory and require validation.