{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:47:55Z","timestamp":1782910075796,"version":"3.54.5"},"reference-count":24,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"fundamental research funds for the provincial universities in Heilongjiang province","award":["2024-KYYWF-0181"],"award-info":[{"award-number":["2024-KYYWF-0181"]}]},{"name":"fundamental research funds for the provincial universities in Heilongjiang province","award":["2024-KYYWF-0197"],"award-info":[{"award-number":["2024-KYYWF-0197"]}]},{"name":"Medical and Health Research Project of Heilongjiang Province","award":["20240404110048"],"award-info":[{"award-number":["20240404110048"]}]},{"name":"Medical and Health Research Project of Heilongjiang Province","award":["20240303070008"],"award-info":[{"award-number":["20240303070008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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-1\u03b1 (MIP-1\u03b1) and MIP-1\u03b2; interleukin (IL)-1\u03b1, IL-1\u03b2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, and IL-17; interferon (IFN)-\u03b1 and IFN-\u03b3; tumor necrosis factor-\u03b1 (TNF-\u03b1); 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\u2013Whitney U test was applied for non-normally distributed data. Group comparisons were performed using independent-samples t-tests or Mann\u2013Whitney U tests for continuous variables and \u03c72 tests or Fisher\u2019s exact tests for categorical variables. The Benjamini\u2013Hochberg 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 &lt; 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\u20130.803, p = 0.025) and 0.657 (95% CI 0.540\u20130.774, p = 0.032), while MCP-1 and operative duration demonstrated modest discriminatory performance, with AUC values of 0.716 (95% CI 0.595\u20130.838, p = 0.003) and 0.708 (95% CI 0.578\u20130.838, 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.<\/jats:p>","DOI":"10.3390\/jcm15135119","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T10:41:01Z","timestamp":1782902461000},"page":"5119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intraoperative Cytokines and Postcraniotomy Infection in Benign Brain Tumors: An Exploratory Prospective Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1200-811X","authenticated-orcid":false,"given":"Mingfei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjuan","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Pi","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pan, X.F., Haishaer, D., Liu, M., Zhou, S.B., Na, H., and Zhao, H.M. (2024). Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection. Cytokine, 179.","DOI":"10.1016\/j.cyto.2024.156593"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, C., Zhang, B.Y., Yu, S.L., Sun, F., Ruan, Q.L., Zhang, W.H., Shao, L.Y., and Chen, S. (2014). The incidence and risk factors of meningitis after major craniotomy in China: A retrospective cohort study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101961"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jinf.2016.09.007","article-title":"Adults with suspected central nervous system infection: A prospective study of diagnostic accuracy","volume":"74","author":"Khatib","year":"2017","journal-title":"J. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yu, Y., and Li, H.J. (2017). Diagnostic and prognostic value of procalcitonin for early intracranial infection after craniotomy. Braz. J. Med. Biol. Res., 50.","DOI":"10.1590\/1414-431x20176021"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s12028-018-0657-y","article-title":"Daptomycin plasma and CSF levels in patients with Healthcare-Associated Meningitis","volume":"31","author":"Piva","year":"2019","journal-title":"Neurocrit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.cmi.2017.07.015","article-title":"Central nervous system infections: Work in progress","volume":"23","author":"Tattevin","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Weng, C., Jiang, T., Jiang, L.W., and Liu, Z.J. (2025). Risk factors for post-craniotomy intracranial infections: A retrospective analysis of 742 cases. Acta. Neurol. Belg.","DOI":"10.1007\/s13760-025-02930-9"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Jiang, D., and Li, Y. (2025). Unraveling the immunosuppressive microenvironment of glioblastoma and advancements in treatment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1590781"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kalluri, A.L., Shah, P.P., and Lim, M. (2023). The Tumor Immune Microenvironment in Primary CNS Neoplasms: A Review of Current Knowledge and Therapeutic Approaches. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032020"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/0004563215589381","article-title":"Interleukin-6 in cerebrospinal fluid as a biomarker of acute meningitis","volume":"53","author":"Prieto","year":"2016","journal-title":"Ann. Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/ANA.0000000000000496","article-title":"Inflammatory markers in serum and cerebrospinal fluid for early detection of external ventricular Drain-associated ventriculitis in patients with subarachnoid hemorrhage","volume":"31","author":"Lenski","year":"2019","journal-title":"J. Neurosurg. Anesthesiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/02688697.2016.1253827","article-title":"Post-craniotomy intracranial infection in patients with brain tumors: A retrospective analysis of 5723 consecutive patients","volume":"31","author":"Shi","year":"2017","journal-title":"Br. J. Neurosurg."},{"key":"ref_13","first-page":"2","article-title":"Expert Consensus on the Diagnosis and Treatment of Central Nervous System Infections in Neurosurgery China (2021 Edition)","volume":"37","author":"Wang","year":"2021","journal-title":"Chin. J. Neurosurg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11060-023-04294-7","article-title":"Additive risk of surgical site infection from more than one risk factor following craniotomy for tumor","volume":"162","author":"Maayan","year":"2023","journal-title":"J. Neuro-Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Li, Y.T., Wang, Y.C., Lee, H.L., Tsao, S.C., Lu, M.C., and Yang, S.F. (2019). Monocyte chemoattractant protein-1, a possible biomarker of multiorgan failure and mortality in ventilator-associated pneumonia. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092218"},{"key":"ref_16","unstructured":"Luo, Y.Y., and Wang, X.P. (2022). Analysis on relationship between levels of sPD-L1, MCP-1 and CD64 index with complicating infections after intracranial tumor resection. Int. J. Lab. Med., 43."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Singh, S., Anshita, D., and Ravichandiran, V. (2021). MCP-1: Function, regulation, and involvement in disease. Int. Immunopharmacol., 101.","DOI":"10.1016\/j.intimp.2021.107598"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neuroscience.2020.03.008","article-title":"IL-4 Switches Microglia\/macrophage M1\/M2 Polarization and Alleviates Neurological Damage by Modulating the JAK1\/STAT6 Pathway Following ICH","volume":"437","author":"He","year":"2020","journal-title":"Neuroscience"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Keegan, A.D., Leonard, W.J., and Zhu, J. (2021). Recent advances in understanding the role of IL-4 signaling. Fac. Rev., 10.","DOI":"10.12703\/r\/10-71"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1016\/j.trecan.2021.06.007","article-title":"Immunity beyond cancer cells: Perspective from tumor tissue","volume":"7","author":"Gao","year":"2021","journal-title":"Trends Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4865","DOI":"10.2147\/IDR.S483985","article-title":"An Investigation into Diagnostic Strategies for Central Nervous System Infections Through the Integration of Metagenomic Next-Generation Sequencing and Conventional Diagnostic Methods","volume":"17","author":"Zhang","year":"2024","journal-title":"Infect. Drug Resist."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s11060-024-04887-w","article-title":"Length of stay following elective craniotomy for tumor resection in children and young adults: A retrospective case series","volume":"171","author":"Lesha","year":"2025","journal-title":"J. Neuro-Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Hasan, M., Diep, D., Manoranjan, B., Maharaj, A., Chaudhry, S., Shaheen, S., Farrokhyar, F., Fleming, A.J., Ajani, O., and Singh, S.K. (2020). Analysis of factors that influence neurosurgical length of hospital stay among newly diagnosed pediatric brain tumor patients. Pediatr. Blood Cancer, 67.","DOI":"10.1002\/pbc.28041"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Phillips, K.R., Enriquez-Marulanda, A., Mackel, C., Ogbonna, J., Moore, J.M., Vega, R.A., and Alterman, R.L. (2023). Predictors of extended length of stay related to craniotomy for tumor resection. World Neurosurg. 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