儿童阻塞性睡眠呼吸暂停综合征患儿血清IL-35和IL-37水平的研究
Serum IL-35 and IL-37 Levels in Pediatrics with Obstructive Sleep Apnea Syndrome
DOI: 10.12677/ACM.2021.111039, PDF,   
作者: 李栋才：深圳市龙岗耳鼻咽喉医院，深圳耳鼻咽喉研究所，广东 深圳；程涵蓉*, 魏永莉：深圳市人民医院呼吸疾病研究所；南方科技大学第一附属医院，暨南大学第二临床医学院，广东 深圳
关键词: 白细胞介素-35；白细胞介素-37；阻塞性睡眠呼吸暂停综合征；炎症；Interleukin-35； Interleukin-37； Obstructive Sleep Apnea Syndrome； In?ammation
摘要: 目的：探讨儿童OSAS患者血清的IL-35、IL-37的水平。方法：46例新诊断的OSAS患者和35例非呼吸暂停对照者被纳入本研究。人口学资料，既往神经肌肉病、遗传代谢病及药物史，习惯通过标准化问卷获得。所有患者均接受多导睡眠图评估。OSAS组平均年龄6.8 ± 3.3(5~9.5)岁。OSAS组中位呼吸暂停低通气指数为12.5 (6.5~21)，中位体重指数为20.5 (18~24.2)。采用ELISA法检测血清IL-35和IL-37水平。结果：OSAS患者血清IL-35和IL-37水平均明显低于健康人。随着OSAS疾病的程度加重，血清IL-35、IL-37水平进一步降低，其差异也具有统计学意义。结论：本研究提示血清IL-35和IL-37可能是OSAS的新的生物标志物，提示调节这两种细胞因子的表达可能为OSAS的治疗提供新的可能靶点。
Abstract: Objective: The aim of the present study was to investigate the serum level of IL-35. IL-37 in patients with OSAS. Methods: 46 newly diagnosed pediatrics OSAS patients and 35 non-apneic controls were enrolled in this study. Demographic data, previous history of diseases including metabolic diseases and drugs, and habits were obtained by a standardized questionnaire. All patients underwent polysomnographic evaluation. The mean age was 6.8 ± 3.3 (5~9.5) years in the OSAS group. Median apnea-hypopnea index was 12.5 (6.5~21) and median body mass index was 20.5 (18~24.2) in the OSAS group. Cytokine levels in serum were determined using ELISA. Results: The results showed that serums IL-35 and IL-37 levels were significantly decreased in OSAS patients compared with healthy subjects. The cytokine levels correlated inversely with OSAS severity. Conclusion: The study showed that serums IL-35 and IL-37 might be potentially novel biomarkers for OSAS, suggesting that regulating the expression of the two cytokines may provide a new possible target for the treatment of OSAS.
文章引用：李栋才, 程涵蓉, 魏永莉. 儿童阻塞性睡眠呼吸暂停综合征患儿血清IL-35和IL-37水平的研究[J]. 临床医学进展, 2021, 11(1): 268-274. https://doi.org/10.12677/ACM.2021.111039

参考文献

[1] Taioufis, C., Thornopoulos, K., Dimitriadis, K., Anastasia, A., Dimitris, T., Christodoulos, S., et al. (2007) The Incremental Effect of Obstructive Sleep Apnoea Syndrome on Arterial Stiffness in Newly Diagnosed Essential Hypertensive Subjects. Journal of Hypertension, 26, 141-146. [Google Scholar] [CrossRef] 
[2] Bhushan, B., Guleria, R., Misra, A., Pandey, R.M., Luthra, K., Vikram, N.K., et al. (2009) Obstructive Sleep Apnoea Correlates with C-Reactive Protein in Obese Asian Indians. Nutrition, Metabolism and Cardiovascular Diseases, 19, 184-189. [Google Scholar] [CrossRef] [PubMed]
[3] Collison, L.W., Workman, C.J., Kuo, T.T., Boyd, K., Wang, Y., Vignali, K.M., et al. (2007) The Inhibitory Cytokine IL-35 Contributes to Regulatory T-Cell Function. Nature, 450, 566-569. [Google Scholar] [CrossRef] [PubMed]
[4] Chaturvedi, V., Collison, L.W., Guy, C.S., Workman, C.J. and Vignali, D.A.A. (2011) Cutting Edge: Human Regulatory T Cells Require IL-35 to Mediate Suppression and Infectious Tolerance. Journal of Immunology, 186, 6661-6666. [Google Scholar] [CrossRef] [PubMed]
[5] Li, X., Mai, J., Virtue, A., Yin, Y., Gong, R., Sha, X., et al. (2012) IL-35 Is a Novel Responsive Anti-Inflammatory Cytokine—A New System of Categorizing Anti-Inflammatory Cytokines. PLoS ONE, 7, e33628. [Google Scholar] [CrossRef] [PubMed]
[6] Lee, Y.K. and Mazmanian, S.K. (2010) Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System? Science, 330, 1768-1773. [Google Scholar] [CrossRef] [PubMed]
[7] Chen, P. and Fang, S. (2004) The Expression of Human Antimicrobial Peptide LL-37 in the Human Nasal Mucosa. The American Journal of Rhinology, 18, 381-385. [Google Scholar] [CrossRef] [PubMed]
[8] Guilleminault, C., Tilkian, A. and Dement, W.C. (1976) The Sleep Apnea Syndromes. Annual Review of Medicine, 27, 465-484. [Google Scholar] [CrossRef] [PubMed]
[9] Marcus, C.L., Brooks, L.J., Draper, K.A., Gozal, D., Halbower, A.C., Jones, J., et al. (2012) Diagnosis and Management of Childhood Obstructive Sleep Apnea Syndrome, Pediatrics, 130, 576-584. [Google Scholar] [CrossRef] [PubMed]
[10] 中华医学会呼吸病学分会睡眠呼吸障碍学组. 阻塞性睡眠呼吸暂停低通气合征诊治指南(2011年修订版)[J].中华结核和呼吸杂志, 2012, 35(1): 9-12.
[11] De Luca Canto, G., Pacheco-Pereira, C., Aydinoz, S., Major, P.W., Flores Mir, C. and Gozal, D. (2014) Biomarkers Associated with Obstructive Sleep Apnea: A Scoping Review. Sleep Medicine Reviews, 23, 28-45. [Google Scholar] [CrossRef] [PubMed]
[12] Katz, E.S. and D’Ambrosio, C.M. (2010) Pediatric Obstructive Sleep Apnea Syndrome. Clinics in Chest Medicine, 31, 221-234. [Google Scholar] [CrossRef] [PubMed]
[13] Farber, J.M. (2002) Clinical Practice Guideline: Diagnosis and Management of Childhood Obstructive Sleep Apnea Syndrome. Pediatrics, 110, 1255-1257. [Google Scholar] [CrossRef] [PubMed]
[14] Ryan, S., Taylor, C.T. and McNicholas, W.T. (2009) Systemic Inflammation: A Key Factor in the Pathogenesis of Cardiovascular Complications in Obstructive Sleep Apnoea Syndrome. Thorax, 64, 631-636.
[15] Minoguchi, K., Tazaki, T., Yokoe, T., Minoguchi, H., Watanabe, Y., Yamamoto, M., et al. (2004) Elevated Production of Tumor Necrosis Factor-Alpha by Monocytes in Patients with Obstructive Sleep Apnea Syndrome. Chest, 126, 1473-1479. [Google Scholar] [CrossRef] [PubMed]
[16] Lui, M.M., Lam, J.C., Mak, H.K., Xu, A., Ooi, C., Lam, D.C., et al. (2009) C-Reactive Protein Is Associated with Obstructive Sleep Apnea Independent of Visceral Obesity. Chest, 135, 950-956. [Google Scholar] [CrossRef] [PubMed]
[17] Mehra, R., Storfer-Isser, A., Kirchner, H.L., Johnson, N., Jenny, N., Tracy, R.P., et al. (2006) Soluble Interleukin 6 Receptor: A Novel Marker of Moderate to Severe Sleep-Related Breathing Disorder. Archives of Internal Medicine, 166, 1725-1731. [Google Scholar] [CrossRef] [PubMed]
[18] Nural, S., Gunay, E., Halici, B., Celik, S. and Unlu, M. (2013) Inflammatory Processes and Effects of Continuous Positive Airway Pressure (CPAP) in Overlap Syndrome. Inflammation, 36, 66-74. [Google Scholar] [CrossRef] [PubMed]
[19] Svensson, M., Venge, P., Janson, C. and Lindberg, E. (2012) Relationship between Sleep-Disordered Breathing and Markers of Systemic Inflammation in Women from the General Population. Journal of Sleep Research, 21, 147-154. [Google Scholar] [CrossRef] [PubMed]
[20] Yokoe, T., Minoguchi, K., Matsuo, H., Oda, N., Minoguchi, H., Yoshino, G., et al. (2003) Elevated Levels of C-Reactive Protein Andinterleukin-6 in Patients with Obstructive Sleep Apnea Syndrome Are Decreased by Nasal Continuous Positive Airway Pressure. Circulation, 107, 1129-1134. [Google Scholar] [CrossRef] 
[21] Vgontzas, A.N., Papanicolaou, D.A., Bixler, E.O., Kales, A., Tyson, K. and Chrousos, G.P. (1997) Elevation of Plasma Cytokines in Disorders of Excessive Daytime Sleepiness: Role of Sleep Disturbance and Obesity. The Journal of Clinical Endocrinology and Metabolism, 82, 1313-1316. [Google Scholar] [CrossRef] [PubMed]
[22] Zandian, M., Mott, K.R., Allen, S.J., Dumitrascu, O., Kuo, J.Z. and Ghiasi, H. (2011) Use of Cytokine Immunotherapy to Block CNS Demyelination Induced by a Recombinant HSV-1 Expressing IL-2. Gene Therapy, 18, 734-742. [Google Scholar] [CrossRef] [PubMed]
[23] Kochetkova, I., Golden, S., Holderness, K., Callis, G. and Pascual, D.W. (2010) IL-35 Stimulation of CD39+ Regulatory T Cells Confers Protection against Collagen II-Induced Arthritis via the Production of IL-10. Journal of Immunology, 184, 7144-7153. [Google Scholar] [CrossRef] [PubMed]
[24] Whitehead, G.S., Wilson, R.H., Nakano, K., Burch, L.H., Nakano, H. and Cook, D.N. (2012) IL-35 Production by Inducible Costimulator (ICOS)-Positive Regulatory T Cells Reverses Established IL-17-Dependent Allergic Airways Disease. Journal of Allergy and Clinical Immunology, 129, 207-215.E5. [Google Scholar] [CrossRef] [PubMed]
[25] Wirtz, S., Billmeier, U., McHedlidze, T., Blumberg, R.S. and Neurath, M.F. (2011) Interleukin-35 Mediates Mucosal Immune Responses That Protect against T-Cell-Dependent Colitis. Gastroenterology, 141, 1875-1886. [Google Scholar] [CrossRef] [PubMed]
[26] Devergne, O., Birkenbach, M. and Kieff, E. (1997) Epstein-Barr Virus-Induced Gene 3 and the p35 Subunit of Interleukin 12 form a Novel Heterodimeric Hematopoietin. Proceedings of the National Academy of Sciences of the United States of America, 94, 12041-12046. [Google Scholar] [CrossRef] [PubMed]
[27] Yang, J., Yang, M., Htut, T.M., Ouyang, X., Hanidu, A., Li, X., et al. (2008) Epstein-Barr Virus-Induced Gene 3 Negatively Regulates IL-17, IL-22 and ROR𝛾t. European Journal of Immunology, 38, 1204-1214. [Google Scholar] [CrossRef] [PubMed]
[28] Frank, G.M., Divito, S.J., Maker, D.M., Xu, M. and Hendricks, R.L. (2010) A Novel P40-Independent Function of IL-12P35 Is Required for Progression and Maintenance of Herpes Stromal Keratitis. Investigative Ophthalmology and Visual Science, 51, 3591-3598. [Google Scholar] [CrossRef] [PubMed]
[29] Ye, S., Wu, J., Zhou, L., Lv, Z., Xie, H. and Zheng, S. (2013) Interleukin-35: The Future of Hyperimmune-Related Diseases? Journal of Interferon and Cytokine Research, 33, 285-291. [Google Scholar] [CrossRef] [PubMed]
[30] Collison, L.W., Delgoffe, G.M., Guy, C.S., Vignali, K.M., Chaturvedi, V., Fairweather, D.L., et al. (2012) The Composition and Signaling of the IL-35 Receptor Are Unconventional. Nature Immunology, 13, 290-299. [Google Scholar] [CrossRef] [PubMed]
[31] Nold, M.F., Nold-Petry, C.A., Zepp, J.A., Palmer, B.E., Bufler, P. and Dinarello, C.A. (2010) IL-37 Is a Fundamental Inhibitor of Innate Immunity. Nature Immunology, 11, 1014-1022. [Google Scholar] [CrossRef] [PubMed]
[32] Boraschi, D., Lucchesi, D., Hainzl, S., Leitner, M., Maier, E., Mangelberger, D., et al. (2011) IL-37: A New Anti-Inflammatory Cytokine of the IL-1 Family. European Cytokine Network, 22, 127-147.
https://www.jle.com/10.1684/ecn.2011.0288
[33] de Smet, K. and Contreras, R. (2005) Human Antimicrobial Peptides: Defensins, Cathelicidins and Histatins. Biotechnology Letters, 27, 1337-1347. [Google Scholar] [CrossRef] [PubMed]

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