新型冠状病毒感染患者血清TH1、TH2和TH17相关细胞因子水平:Meta分析
The Level of Serum TH1, TH2 and TH17-Related Cytokines in Patients with COVID-19 Infection: A Meta-Analysis
DOI: 10.12677/acm.2024.14102833, PDF,   
作者: 徐国超, 杨 丹*:贵州医科大学临床医学院,贵州 贵阳;杜龙平:大理大学临床医学院,云南 大理
关键词: 新型冠状病毒TH1TH2TH17Meta分析细胞因子COVID-19 TH1 TH2 TH17 Meta-Analysis Cytokines
摘要: 目的:本研究采用Meta分析方法,系统评估了COVID‐19患者外周血中TH1、TH2、TH17相关细胞因子水平,并深入探讨了这些细胞因子研究结果存在差异的原因。方法:本研究已通过国际荟萃分析INPLASY平台认证(INPLASY协议认证编号:202380023),通过检索中国知网、PubMed、Embase、Cochrane和Web of Science数据库,收集COVID-19患者和健康对照群体外周血TH1、TH2、TH17相关细胞因子(TNF-a、IL-2、IL-4、IL-10、IL-17)水平的病例对照研究,检索时间范围为建库至2023年10月10日。由研究者独立完成文献筛选、数据提取和偏倚评估,使用RevMan 5.4软件进行Meta分析。结果:该Meta分析共检索出19,941项研究,最终纳入了6项进行Meta分析,这些研究均为中、高质量文献。患者入组的时间范围从2020年~2022年不等。结果表明:COVID-19感染组的患者外周血TNF-a水平显著高于健康对照组(HC组) [MD = 3.42, 95%CI (1.91, 4.92), I2 = 50%, P < 0.00001];COVID-19感染组患者外周血IL-4水平显著高于健康对照组(HC组) [MD = 2.21, 95%CI (0.99, 3.42), I2 = 98%, P = 0.0004];COVID-19感染组患者外周血IL-10水平显著高于健康对照组(HC组) [MD = 3.38, 95%CI (1.97, 4.80), I2 = 84%, P < 0.00001];COVID-19感染组患者外周血IL-17水平显著高于健康对照组(HC组) [MD = 5.94, 95%CI (1.50, 10.39), I2 = 98%, P = 0.009];COVID-19感染组患者与HC组外周血IL-2水平差异无统计学意义[MD = 0.89, 95%CI (−2.19, 3.97), I2 = 67%, P = 0.57]。结论:一些与TH1、TH2及TH17相关的细胞因子在COVID-19患者外周血中的水平明显高于健康对照组,这些细胞因子在新型冠状病毒感染的疾病进展中起着重要作用。
Abstract: Objective: In this study, we used Meta-analysis to systematically evaluate the levels of TH1, TH2, and TH17-related cytokines in the peripheral blood of COVID-19 patients, and the reasons for the differences in the findings of these cytokines were explored in depth. Methods: This study has been validated by the international Meta-analysis INPLASY platform (INPLASY protocol certification number: 202380023), by searching China Knowledge, PubMed, Embase, Cochrane and Web of Science databases, a case-control study on the levels of TH1, TH2, and TH17-related cytokines (TNFa, IL-2, IL-4, IL-10, and IL-17) in peripheral blood of COVID-19 patients and healthy control groups was collected, with a search timeframe from library construction to October 10, 2023. Literature screening, data extraction and bias assessment were done independently by the authors, and Meta-analysis was performed using RevMan 5.4 software. Results: The Meta-analysis retrieved a total of 19,941 studies, and 6 were finally included for Meta-analysis, which were all medium- and high-quality literature. The time of patient enrollment ranged from 2020 to 2022. The results showed that patients in the COVID-19-infected group had significantly higher peripheral blood TNF-a levels than in the healthy control group (HC group) [MD = 3.42, 95%CI (1.91, 4.92), I2 = 50%, P < 0.00001]; peripheral blood IL-4 levels were significantly higher in patients in the COVID-19-infected group than in the healthy control group (HC group) [MD = 2.21, 95%CI (0.99, 3.42), I2 = 98%, P = 0.0004]; peripheral blood IL-10 levels were significantly higher in patients in the COVID-19-infected group than in the healthy control group (HC group) [MD = 3.38, 95%CI (1.97, 4.80), I2 = 84%, P <0.00001]; peripheral blood IL-17 levels were significantly higher in patients in the COVID-19-infected group than in the healthy control group (HC group) [MD = 5.94, 95%CI (1.50, 10.39), I2 = 98%, P = 0.009]; the difference in peripheral blood IL-2 levels between patients in the COVID-19-infected group and the HC group was not statistically significant [MD = 0.89, 95%CI (−2.19, 3.97), I2 =67%, P = 0.57]. Conclusion: Some cytokines related to TH1, TH2 and TH17 were significantly higher in the peripheral blood of COVID-19 patients than in the healthy control group, and these cytokines play an important role in the disease progression of novel coronavirus infections.
文章引用:徐国超, 杨丹, 杜龙平. 新型冠状病毒感染患者血清TH1、TH2和TH17相关细胞因子水平:Meta分析[J]. 临床医学进展, 2024, 14(10): 1575-1584. https://doi.org/10.12677/acm.2024.14102833

参考文献

[1] 高乐女, 黄运生, 王勇. 武汉地区57例新型冠状病毒肺炎的临床特征及中医证候初探[J]. 江西中医药大学学报, 2023, 35(2): 41-44.
[2] Anka, A.U., Tahir, M.I., Abubakar, S.D., Alsabbagh, M., Zian, Z., Hamedifar, H., et al. (2020) Coronavirus Disease 2019 (COVID‐19): An Overview of the Immunopathology, Serological Diagnosis and Management. Scandinavian Journal of Immunology, 93, e12998. [Google Scholar] [CrossRef] [PubMed]
[3] Del Valle, D.M., Kim-Schulze, S., Huang, H., Beckmann, N.D., Nirenberg, S., Wang, B., et al. (2020) An Inflammatory Cytokine Signature Predicts COVID-19 Severity and Survival. Nature Medicine, 26, 1636-1643. [Google Scholar] [CrossRef] [PubMed]
[4] Hasanvand, A. (2022) COVID-19 and the Role of Cytokines in This Disease. Inflammopharmacology, 30, 789-798. [Google Scholar] [CrossRef] [PubMed]
[5] Channappanavar, R. and Perlman, S. (2017) Pathogenic Human Coronavirus Infections: Causes and Consequences of Cytokine Storm and Immunopathology. Seminars in Immunopathology, 39, 529-539. [Google Scholar] [CrossRef] [PubMed]
[6] Kalantar, K., Ghamar Talepoor, A., Eshkevar Vakili, M., Karami, N., Kalani, M., Ghandehari, F., et al. (2023) Th-1, Th-2, Th-9, Th-17, Th-22 Type Cytokine Concentrations of Critical COVID-19 Patients after Treatment with Remdesivir. Immunobiology, 228, Article ID: 152378. [Google Scholar] [CrossRef] [PubMed]
[7] 崔艳花. 新型冠状病毒肺炎患者细胞因子的动态变化与住院时长的相关性[J]. 河南医学高等专科学校学报, 2022, 34(6): 688-692.
[8] Smail, S.W., Babaei, E., Amin, K. and Abdulahad, W.H. (2023) Serum IL-23, IL-10, and TNF-α Predict In-Hospital Mortality in COVID-19 Patients. Frontiers in Immunology, 14, Article ID: 1145840. [Google Scholar] [CrossRef] [PubMed]
[9] Ahearn‐Ford, S., Lunjani, N., McSharry, B., MacSharry, J., Fanning, L., Murphy, G., et al. (2021) Long‐Term Disruption of Cytokine Signalling Networks Is Evident in Patients Who Required Hospitalization for SARS‐COV‐2 Infection. Allergy, 76, 2910-2913. [Google Scholar] [CrossRef] [PubMed]
[10] Han, H., Ma, Q., Li, C., Liu, R., Zhao, L., Wang, W., et al. (2020) Profiling Serum Cytokines in COVID-19 Patients Reveals IL-6 and IL-10 Are Disease Severity Predictors. Emerging Microbes & Infections, 9, 1123-1130. [Google Scholar] [CrossRef] [PubMed]
[11] Lu, Q., Zhu, Z., Tan, C., Zhou, H., Hu, Y., Shen, G., et al. (2021) Changes of Serum IL‐10, IL‐1β, IL‐6, MCP‐1, TNF‐α, IP‐10 and IL‐4 in COVID‐19 Patients. International Journal of Clinical Practice, 75, e14462. [Google Scholar] [CrossRef] [PubMed]
[12] 罗斯威, 姚亚超, 钟丽梅, 等. 新冠肺炎患者和细菌性肺炎患者血清差异表达的细胞因子特征分析[J]. 新医学, 2022, 53(5): 372-378.
[13] 董艳迎, 李妙羡, 朱建宏, 等. 新型冠状病毒肺炎患者实验室检测指标与免疫学特征分析[J]. 分子诊断与治疗杂志, 2020, 12(6): 697-700+714.
[14] 黄春明, 詹远京, 胡中伟. 入院时CT正常新型冠状病毒感染者淋巴细胞亚群和细胞因子特点及临床意义[J]. 实用医学杂志, 2020, 36(23): 3179-3183.
[15] 杨文. T淋巴细胞亚群检测, 帮助了解你的免疫力[J]. 家庭医药, 2023(7): 75.
[16] Hu, B., Huang, S. and Yin, L. (2020) The Cytokine Storm and COVID‐19. Journal of Medical Virology, 93, 250-256. [Google Scholar] [CrossRef] [PubMed]
[17] Talaat, R.M., Mohamed, S.F., Bassyouni, I.H. and Raouf, A.A. (2015) Th1/Th2/Th17/Treg Cytokine Imbalance in Systemic Lupus Erythematosus (SLE) Patients: Correlation with Disease Activity. Cytokine, 72, 146-153. [Google Scholar] [CrossRef] [PubMed]
[18] De Biasi, S., Meschiari, M., Gibellini, L., Bellinazzi, C., Borella, R., Fidanza, L., et al. (2020) Marked T Cell Activation, Senescence, Exhaustion and Skewing towards TH17 in Patients with COVID-19 Pneumonia. Nature Communications, 11, Article No. 3434. [Google Scholar] [CrossRef] [PubMed]
[19] Kasuga, Y., Zhu, B., Jang, K. and Yoo, J. (2021) Innate Immune Sensing of Coronavirus and Viral Evasion Strategies. Experimental & Molecular Medicine, 53, 723-736. [Google Scholar] [CrossRef] [PubMed]
[20] Fiorucci, G., Chiantore, M.V., Mangino, G. and Romeo, G. (2015) MicroRNAs in Virus-Induced Tumorigenesis and IFN System. Cytokine & Growth Factor Reviews, 26, 183-194. [Google Scholar] [CrossRef] [PubMed]
[21] Gadotti, A.C., de Castro Deus, M., Telles, J.P., Wind, R., Goes, M., Garcia Charello Ossoski, R., et al. (2020) IFN-γ Is an Independent Risk Factor Associated with Mortality in Patients with Moderate and Severe COVID-19 Infection. Virus Research, 289, Article ID: 198171. [Google Scholar] [CrossRef] [PubMed]
[22] Lucas, C., Wong, P., Klein, J., Castro, T.B.R., Silva, J., Sundaram, M., et al. (2020) Longitudinal Analyses Reveal Immunological Misfiring in Severe COVID-19. Nature, 584, 463-469. [Google Scholar] [CrossRef] [PubMed]
[23] Alhajjat, A.M., Redden, C.R., Langereis, M., Papastefan, S.T., Ito, J.A.S., Ott, K.C., et al. (2023) CD4 and IL-2 Mediated NK Cell Responses after COVID-19 Infection and mRNA Vaccination in Adults. Immunobiology, 228, Article ID: 152304. [Google Scholar] [CrossRef] [PubMed]
[24] Liao, W., Lin, J. and Leonard, W.J. (2011) IL-2 Family Cytokines: New Insights into the Complex Roles of IL-2 as a Broad Regulator of T Helper Cell Differentiation. Current Opinion in Immunology, 23, 598-604. [Google Scholar] [CrossRef] [PubMed]
[25] Zhang, Q., Wang, L., Wang, S., Cheng, H., Xu, L., Pei, G., et al. (2022) Signaling Pathways and Targeted Therapy for Myocardial Infarction. Signal Transduction and Targeted Therapy, 7, Article No. 78. [Google Scholar] [CrossRef] [PubMed]
[26] Kabata, H., Moro, K. and Koyasu, S. (2018) The Group 2 Innate Lymphoid Cell (ILC2) Regulatory Network and Its Underlying Mechanisms. Immunological Reviews, 286, 37-52. [Google Scholar] [CrossRef] [PubMed]
[27] Wu, J., Chen, S. and Li, X. (2023) Correlation between B-Cell Lymphoma 6 with the Balance of T Helper-1/2 and Severity of Allergic Rhinitis. Allergologia et Immunopathologia, 51, 1-8. [Google Scholar] [CrossRef] [PubMed]
[28] Spangler, J.B., Moraga, I., Jude, K.M., Savvides, C.S. and Garcia, K.C. (2019) A Strategy for the Selection of Monovalent Antibodies That Span Protein Dimer Interfaces. Journal of Biological Chemistry, 294, 13876-13886. [Google Scholar] [CrossRef] [PubMed]
[29] Tsiogka, A., Kyriazopoulou, M., Kontochristopoulos, G., Nicolaidou, E., Stratigos, A., Rigopoulos, D., et al. (2022) The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review. Journal of Clinical Medicine, 11, Article 4431. [Google Scholar] [CrossRef] [PubMed]
[30] Shih, L., Yang, C., Liao, M., Lu, K., Hu, W. and Lin, C. (2023) An Important Call: Suggestion of Using IL-10 as Therapeutic Agent for COVID-19 with ARDS and Other Complications. Virulence, 14, Article ID: 2190650. [Google Scholar] [CrossRef] [PubMed]
[31] Berry, S.P.D., Dossou, C., Kashif, A., Sharifinejad, N., Azizi, G., Hamedifar, H., et al. (2022) The Role of IL-17 and Anti-Il-17 Agents in the Immunopathogenesis and Management of Autoimmune and Inflammatory Diseases. International Immunopharmacology, 102, Article ID: 108402. [Google Scholar] [CrossRef] [PubMed]
[32] Muyayalo, K.P., Huang, D., Zhao, S., Xie, T., Mor, G. and Liao, A. (2020) COVID‐19 and Treg/Th17 Imbalance: Potential Relationship to Pregnancy Outcomes. American Journal of Reproductive Immunology, 84, e13304. [Google Scholar] [CrossRef] [PubMed]
[33] Martonik, D., Parfieniuk-Kowerda, A., Rogalska, M. and Flisiak, R. (2021) The Role of Th17 Response in COVID-19. Cells, 10, Article 1550. [Google Scholar] [CrossRef] [PubMed]