细胞因子在脓毒症严重程度评估及预后预测中的研究进展
Research Progress of Cytokines in Severity Assessment and Prognosis Prediction of Sepsis
DOI: 10.12677/acm.2025.152381, PDF,    科研立项经费支持
作者: 胡希明*, 李玉翠:右江民族医学院研究生学院,广西 百色;李 军#:右江民族医学院附属医院重症医学科,广西 百色
关键词: 脓毒症细胞因子严重程度预后全身炎症反应综合征代偿性抗炎反应综合征Sepsis Cytokines Order of Severity Prognosis SIRS CARS
摘要: 脓毒症(Sepsis)是宿主对感染反应失调所致危及生命的器官功能障碍,具有高发病率和高死亡率,其进展为严重脓毒症或脓毒性休克时,患者预后通常较差。在脓毒症中,细胞因子通过参与全身炎症反应综合征(SIRS)和代偿性抗炎反应综合征(CARS)发挥重要作用,同时在病情严重程度评估和预后预测中可能成为新型生物标志物。本文综述了细胞因子与脓毒症严重程度评估及预后预测的相关性研究,旨在为未来相关研究及临床转化提供科学依据。
Abstract: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, with a high incidence and mortality rate. When patients progress to severe sepsis or septic shock, the prognosis is usually poor. In sepsis, cytokines play an important role by participating in systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS), and may become novel biomarkers in severity assessment and prognosis prediction. This article reviewed the correlation between cytokines and sepsis severity assessment and prognosis prediction, aiming to provide scientific basis for future related research and clinical transformation.
文章引用:胡希明, 李玉翠, 李军. 细胞因子在脓毒症严重程度评估及预后预测中的研究进展[J]. 临床医学进展, 2025, 15(2): 572-580. https://doi.org/10.12677/acm.2025.152381

参考文献

[1] Fleischmann-Struzek, C. and Rudd, K. (2023) Challenges of Assessing the Burden of Sepsis. Medizinische Klinik-Intensivmedizin und Notfallmedizin, 118, 68-74. [Google Scholar] [CrossRef] [PubMed]
[2] Rudd, K.E., Johnson, S.C., Agesa, K.M., Shackelford, K.A., Tsoi, D., Kievlan, D.R., et al. (2020) Global, Regional, and National Sepsis Incidence and Mortality, 1990-2017: Analysis for the Global Burden of Disease Study. The Lancet, 395, 200-211. [Google Scholar] [CrossRef] [PubMed]
[3] Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., et al. (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315, 801-810. [Google Scholar] [CrossRef] [PubMed]
[4] Liu, C., Chu, D., Kalantar‐Zadeh, K., George, J., Young, H.A. and Liu, G. (2021) Cytokines: From Clinical Significance to Quantification. Advanced Science, 8, e2004433. [Google Scholar] [CrossRef] [PubMed]
[5] Jarczak, D. and Nierhaus, A. (2022) Cytokine Storm—Definition, Causes, and Implications. International Journal of Molecular Sciences, 23, Article No. 11740. [Google Scholar] [CrossRef] [PubMed]
[6] Assinger, A., Schrottmaier, W.C., Salzmann, M. and Rayes, J. (2019) Platelets in Sepsis: An Update on Experimental Models and Clinical Data. Frontiers in Immunology, 10, Article No. 1687. [Google Scholar] [CrossRef] [PubMed]
[7] Shubin, N.J., Monaghan, S.F. and Ayala, A. (2011) Anti-Inflammatory Mechanisms of Sepsis. In: Contributions to Microbiology, S. Karger AG, 108-124. [Google Scholar] [CrossRef] [PubMed]
[8] Clere-Jehl, R., Mariotte, A., Meziani, F., Bahram, S., Georgel, P. and Helms, J. (2020) JAK-STAT Targeting Offers Novel Therapeutic Opportunities in Sepsis. Trends in Molecular Medicine, 26, 987-1002. [Google Scholar] [CrossRef] [PubMed]
[9] Chousterman, B.G., Swirski, F.K. and Weber, G.F. (2017) Cytokine Storm and Sepsis Disease Pathogenesis. Seminars in Immunopathology, 39, 517-528. [Google Scholar] [CrossRef] [PubMed]
[10] Liu, D., Huang, S., Sun, J., Zhang, H., Cai, Q., Gao, C., et al. (2022) Sepsis-Induced Immunosuppression: Mechanisms, Diagnosis and Current Treatment Options. Military Medical Research, 9, Article No. 56. [Google Scholar] [CrossRef] [PubMed]
[11] Wang, X., Zhang, H., Guo, R., Li, X., Liu, H., Wang, Z., et al. (2021) MicroRNA-223 Modulates the IL-4-Medicated Macrophage M2-Type Polarization to Control the Progress of Sepsis. International Immunopharmacology, 96, Article ID: 107783. [Google Scholar] [CrossRef] [PubMed]
[12] Hotchkiss, R.S., Monneret, G. and Payen, D. (2013) Sepsis-Induced Immunosuppression: From Cellular Dysfunctions to Immunotherapy. Nature Reviews Immunology, 13, 862-874. [Google Scholar] [CrossRef] [PubMed]
[13] Schrijver, D.P., Röring, R.J., Deckers, J., de Dreu, A., Toner, Y.C., Prevot, G., et al. (2023) Resolving Sepsis-Induced Immunoparalysis via Trained Immunity by Targeting Interleukin-4 to Myeloid Cells. Nature Biomedical Engineering, 7, 1097-1112. [Google Scholar] [CrossRef] [PubMed]
[14] Song, Z., Zhang, J., Zhang, X., Li, D., Wang, H., Xu, X., et al. (2014) Interleukin 4 Deficiency Reverses Development of Secondary Pseudomonas Aeruginosa Pneumonia during Sepsis-Associated Immunosuppression. Journal of Infectious Diseases, 211, 1616-1627. [Google Scholar] [CrossRef] [PubMed]
[15] Wu, H., Wu, C., Chen, C., Chung, K., Tseng, J., Liu, Y., et al. (2008) The Interleukin-4 Expression in Patients with Severe Sepsis. Journal of Critical Care, 23, 519-524. [Google Scholar] [CrossRef] [PubMed]
[16] Hynninen, M., Pettilä, V., Takkunen, O., Orko, R., Jansson, S., Kuusela, P., et al. (2003) Predictive Value of Monocyte Histocompatibility Leukocyte Antigen-Dr Expression and Plasma Interleukin-4 and-10 Levels in Critically Ill Patients with Sepsis. Shock, 20, 1-4. [Google Scholar] [CrossRef] [PubMed]
[17] Li, J. (2023) Over-Expression of Programmed Death-Ligand 1 and Programmed Death-1 on Antigen-Presenting Cells as a Predictor of Organ Dysfunction and Mortality during Early Sepsis: A Prospective Cohort Study. World Journal of Emergency Medicine, 14, 179-185. [Google Scholar] [CrossRef] [PubMed]
[18] Bozza, F.A., Salluh, J.I., Japiassu, A.M., Soares, M., Assis, E.F., Gomes, R.N., et al. (2007) Cytokine Profiles as Markers of Disease Severity in Sepsis: A Multiplex Analysis. Critical Care, 11, R49. [Google Scholar] [CrossRef] [PubMed]
[19] Ruiz-Rodríguez, J.C., Plata-Menchaca, E.P., Chiscano-Camón, L., Ruiz-Sanmartin, A. and Ferrer, R. (2022) Blood Purification in Sepsis and COVID-19: What’s New in Cytokine and Endotoxin Hemoadsorption. Journal of Anesthesia, Analgesia and Critical Care, 2, Article No. 15. [Google Scholar] [CrossRef] [PubMed]
[20] Mirzarahimi, M., Barak, M., Eslami, A. and Enteshari-Moghaddam, A. (2017) The Role of Interleukin-6 in the Early Diagnosis of Sepsis in Premature Infants. Pediatric Reports, 9, Article No. 7305. [Google Scholar] [CrossRef] [PubMed]
[21] Reis Machado, J., Soave, D.F., da Silva, M.V., de Menezes, L.B., Etchebehere, R.M., Monteiro, M.L.G.d.R., et al. (2014) Neonatal Sepsis and Inflammatory Mediators. Mediators of Inflammation, 2014, Article ID: 269681. [Google Scholar] [CrossRef] [PubMed]
[22] Yende, S., Kellum, J.A., Talisa, V.B., Peck Palmer, O.M., Chang, C.H., Filbin, M.R., et al. (2019) Long-Term Host Immune Response Trajectories among Hospitalized Patients with Sepsis. JAMA Network Open, 2, e198686. [Google Scholar] [CrossRef] [PubMed]
[23] Matsumoto, H., Ogura, H., Shimizu, K., Ikeda, M., Hirose, T., Matsuura, H., et al. (2018) The Clinical Importance of a Cytokine Network in the Acute Phase of Sepsis. Scientific Reports, 8, Article No. 13995. [Google Scholar] [CrossRef] [PubMed]
[24] Memar, M.Y., Alizadeh, N., Varshochi, M. and Kafil, H.S. (2017) Immunologic Biomarkers for Diagnostic of Early-Onset Neonatal Sepsis. The Journal of Maternal-Fetal & Neonatal Medicine, 32, 143-153. [Google Scholar] [CrossRef] [PubMed]
[25] da Fonseca, F.A.M., Espósito, A.P., da Silva, M.H.B.N., Nunes, V.S., Cazita, P.M., Ferreira, G.S., et al. (2022) Monocyte-to-HDL Ratio and Non-HDL Cholesterol Were Predictors of Septic Shock in Newborns. Clinics, 77, Article ID: 100111. [Google Scholar] [CrossRef] [PubMed]
[26] Kumar, A.T., Sudhir, U., Punith, K., Kumar, V.N.R. and Rao, M.Y. (2009) Cytokine Profile in Elderly Patients with Sepsis. Indian Journal of Critical Care Medicine, 13, 74-78. [Google Scholar] [CrossRef] [PubMed]
[27] Matsuura, R., Komaru, Y., Miyamoto, Y., Yoshida, T., Yoshimoto, K., Hamasaki, Y., et al. (2020) Different Biomarker Kinetics in Critically Ill Patients with High Lactate Levels. Diagnostics, 10, Article No. 454. [Google Scholar] [CrossRef] [PubMed]
[28] Davoudian, S., Piovani, D., Desai, A., Mapelli, S.N., Leone, R., Sironi, M., et al. (2022) A Cytokine/PTX3 Prognostic Index as a Predictor of Mortality in Sepsis. Frontiers in Immunology, 13, Article ID: 979232. [Google Scholar] [CrossRef] [PubMed]
[29] Hess, D.A., Trac, J.Z., Glazer, S.A., Terenzi, D.C., Quan, A., Teoh, H., et al. (2020) Vascular Risk Reduction in Obesity through Reduced Granulocyte Burden and Improved Angiogenic Monocyte Content Following Bariatric Surgery. Cell Reports Medicine, 1, Article ID: 100018. [Google Scholar] [CrossRef] [PubMed]
[30] Xiao, L., Ran, X., Zhong, Y., Le, Y. and Li, S. (2022) A Combined Ratio Change of Inflammatory Biomarkers at 72 h Could Predict the Severity and Prognosis of Sepsis from Pulmonary Infections. Immunobiology, 227, Article ID: 152290. [Google Scholar] [CrossRef] [PubMed]
[31] Rau, M., Schiller, M., Krienke, S., Heyder, P., Lorenz, H. and Blank, N. (2010) Clinical Manifestations but Not Cytokine Profiles Differentiate Adult-Onset Still’s Disease and Sepsis. The Journal of Rheumatology, 37, 2369-2376. [Google Scholar] [CrossRef] [PubMed]
[32] Hugo Montes, A., Valle-Garay, E., Martin, G., Collazos, J., Alvarez, V., Meana, A., et al. (2021) The tnf-α (−238 G/A) Polymorphism Could Protect against Development of Severe Sepsis. Innate Immunity, 27, 409-420. [Google Scholar] [CrossRef] [PubMed]
[33] Chaudhry, H., Zhou, J., Zhong, Y., et al. (2013) Role of Cytokines as a Double-Edged Sword in Sepsis. In Vivo, 27, 669-684.
[34] Yin, J., Chen, Y., Huang, J., Yan, L., Kuang, Z., Xue, M., et al. (2021) Prognosis-Related Classification and Dynamic Monitoring of Immune Status in Patients with Sepsis: A Prospective Observational Study. World Journal of Emergency Medicine, 12, 185-191. [Google Scholar] [CrossRef] [PubMed]
[35] Lu, X., Song, C., Wang, P., Li, L., Lin, L., Jiang, S., et al. (2023) The Clinical Trajectory of Peripheral Blood Immune Cell Subsets, T-Cell Activation, and Cytokines in Septic Patients. Inflammation Research, 73, 145-155. [Google Scholar] [CrossRef] [PubMed]
[36] Gogos, C.A., Drosou, E., Bassaris, H.P. and Skoutelis, A. (2000) Pro‐ versus Anti‐Inflammatory Cytokine Profile in Patients with Severe Sepsis: A Marker for Prognosis and Future Therapeutic Options. The Journal of Infectious Diseases, 181, 176-180. [Google Scholar] [CrossRef] [PubMed]
[37] Yin, F., Xi, Y., Wang, Y., Li, B., Qian, J., Ren, H., et al. (2021) The Clinical Outcomes and Biomarker Features of Severe Sepsis/Septic Shock with Severe Neutropenia: A Retrospective Cohort Study. Translational Pediatrics, 10, 464-473. [Google Scholar] [CrossRef] [PubMed]
[38] Zhi, F., Ma, J., Ji, D., Bao, J. and Li, Q. (2024) Causal Associations between Circulating Cytokines and Risk of Sepsis and Related Outcomes: A Two-Sample Mendelian Randomization Study. Frontiers in Immunology, 15, Article ID: 1336586. [Google Scholar] [CrossRef] [PubMed]
[39] Vogeler, M., Schenz, J., Müller, E., Weigand, M. and Fischer, D. (2024) The Immune System of the Critically Ill Patient. Anasthesiol Intensivmed Notfallmed Schmerzther, 59, 96-112.
[40] Nesseler, N., Martin-Chouly, C., Perrichet, H., Ross, J.T., Rousseau, C., Sinha, P., et al. (2019) Low Interleukin-10 Release after ex Vivo Stimulation of Whole Blood Is Associated with Persistent Organ Dysfunction in Sepsis: A Prospective Observational Study. Anaesthesia Critical Care & Pain Medicine, 38, 485-491. [Google Scholar] [CrossRef] [PubMed]
[41] Amatya, N., Garg, A.V. and Gaffen, S.L. (2017) IL-17 Signaling: The Yin and the Yang. Trends in Immunology, 38, 310-322. [Google Scholar] [CrossRef] [PubMed]
[42] Freitas, A., Alves-Filho, J.C., Victoni, T., Secher, T., Lemos, H.P., Sônego, F., et al. (2009) IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis. The Journal of Immunology, 182, 7846-7854. [Google Scholar] [CrossRef] [PubMed]
[43] Pool, R., Gomez, H. and Kellum, J.A. (2018) Mechanisms of Organ Dysfunction in Sepsis. Critical Care Clinics, 34, 63-80. [Google Scholar] [CrossRef] [PubMed]
[44] Zhou, K.L., He, Y.R., Liu, Y.J., Liu, Y.M., Xuan, L.Z., Gu, Z.Y., et al. (2023) Il‐17a/p38 Signaling Pathway Induces Alveolar Epithelial Cell Pyroptosis and Hyperpermeability in Sepsis‐Induced Acute Lung Injury by Activating NLRP3 Inflammasome. Advanced Biology, 7, e2300220. [Google Scholar] [CrossRef] [PubMed]
[45] Rendon, J.L. and Choudhry, M.A. (2012) Th17 Cells: Critical Mediators of Host Responses to Burn Injury and Sepsis. Journal of Leukocyte Biology, 92, 529-538. [Google Scholar] [CrossRef] [PubMed]
[46] Jin, H., Wei, W., Zhao, Y., Ma, A., Sun, K., Lin, X., et al. (2023) The Roles of Interleukin-17a in Risk Stratification and Prognosis of Patients with Sepsis-Associated Acute Kidney Injury. Kidney Research and Clinical Practice, 42, 742-750. [Google Scholar] [CrossRef] [PubMed]
[47] Kassasseya, C., Torsin, L.I., Musset, C., Benhamou, M., Chaudry, I.H., Cavaillon, J., et al. (2024) Divergent Effects of Tumor Necrosis Factor (TNF) in Sepsis: A Meta-Analysis of Experimental Studies. Critical Care, 28, Article No. 293. [Google Scholar] [CrossRef] [PubMed]
[48] Li, X., Liu, M., Fu, Y., Jiang, Y. and Zhang, Z. (2023) Alterations in Levels of Cytokine Following Treatment to Predict Outcome of Sepsis: A Meta-Analysis. Cytokine, 161, Article ID: 156056. [Google Scholar] [CrossRef] [PubMed]
[49] Li, J., Xiao, C. and Zheng, H. (2024) Prognostic Value of Inflammatory Cytokine Detection for Sepsis Patients in ICU: A Meta-Analysis. American Journal of Translational Research, 16, 2612-2621. [Google Scholar] [CrossRef] [PubMed]
[50] Gharamti, A.A., Samara, O., Monzon, A., Montalbano, G., Scherger, S., DeSanto, K., et al. (2022) Proinflammatory Cytokines Levels in Sepsis and Healthy Volunteers, and Tumor Necrosis Factor-Alpha Associated Sepsis Mortality: A Systematic Review and Meta-Analysis. Cytokine, 158, Article ID: 156006. [Google Scholar] [CrossRef] [PubMed]
[51] Orhun, G., Tüzün, E., Özcan, P.E., et al. (2019) Association between Inflammatory Markers and Cognitive Outcome in Patients with Acute Brain Dysfunction Due to Sepsis. Noro Psikiyatri Arsivi, 56, 63-70.
[52] Paraschos, M.D., Patrani, M., Pistiki, A., Katsenos, C., Tsaganos, T., Netea, M.G., et al. (2015) Defective Cytokine Production Early after Multiple Traumas: Modulation in Severe Sepsis. Cytokine, 76, 222-226. [Google Scholar] [CrossRef] [PubMed]
[53] Li, Q., Wu, C., Liu, Z., Zhang, H., Du, Y., Liu, Y., et al. (2019) Increased TLR4 Expression Aggravates Sepsis by Promoting IFN-γ Expression in CD38(-/-) Mice. Journal of Immunology Research, 2019, Article ID: 3737890. [Google Scholar] [CrossRef] [PubMed]
[54] Stassen, N.A., Leslie-Norfleet, L.A., Robertson, A.M., Eichenberger, M.R. and Polk, H.C. (2002) Interferon-γ Gene Polymorphisms and the Development of Sepsis in Patients with Trauma. Surgery, 132, 289-292. [Google Scholar] [CrossRef] [PubMed]
[55] Wang, D., Zhong, X., Huang, D., Chen, R., Bai, G., Li, Q., et al. (2014) Functional Polymorphisms of Interferon-Gamma Affect Pneumonia-Induced Sepsis. PLOS ONE, 9, e87049. [Google Scholar] [CrossRef] [PubMed]
[56] Vucic, J., Vucic, M., Stankovic, T., Stamenkovic, H., Stankovic, S. and Zlatanovic, D. (2021) Potential Role of IFN-γ and IL-5 in Sepsis Prediction of Preterm Neonates. Open Medicine, 16, 139-145. [Google Scholar] [CrossRef] [PubMed]
[57] Payen, D., Faivre, V., Miatello, J., Leentjens, J., Brumpt, C., Tissières, P., et al. (2019) Multicentric Experience with Interferon Gamma Therapy in Sepsis Induced Immunosuppression. a Case Series. BMC Infectious Diseases, 19, Article No. 931. [Google Scholar] [CrossRef] [PubMed]
[58] Romero, C.R., Herzig, D.S., Etogo, A., Nunez, J., Mahmoudizad, R., Fang, G., et al. (2010) The Role of Interferon-γ in the Pathogenesis of Acute Intra-Abdominal Sepsis. Journal of Leukocyte Biology, 88, 725-735. [Google Scholar] [CrossRef] [PubMed]
[59] Qiu, G., Wang, C., Smith, R., Harrison, K. and Yin, K. (2001) Role of IFN-γ in Bacterial Containment in a Model of Intra-Abdominal Sepsis. Shock, 16, 425-429. [Google Scholar] [CrossRef] [PubMed]