儿童肥胖中的慢性低度炎症：关键生物标志物的系统评价与Meta分析

儿童肥胖与慢性低度炎症相关，后者被认为是导致胰岛素抵抗、血脂异常和心血管风险增加的关键机制。已有研究报道肥胖儿童的白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）和高敏C反应蛋白（hs-CRP）水平升高，但研究结果存在矛盾，且目前尚未对这些生物标志物在儿童群体中的水平进行定量汇总分析。

本研究旨在系统梳理肥胖儿童炎症生物标志物的相关数据，并将其水平与对照组进行定量比较。

在PubMed、Scopus、Web of Science、Semantic Scholar、e-Library和Google Scholar数据库中进行了系统的文献检索（截至2025年8月）。纳入的分析对象为观察性研究，这些研究的受试者为6–18岁根据WHO标准或国家标准诊断为肥胖的儿童和青少年，且报告中测定了CRP、hs-CRP、IL-6或TNF-α的水平。

Meta分析共纳入21项研究，总计11,193名参与者。结果显示，肥胖儿童的所有研究涉及的炎症细胞因子水平均显著升高。其中，CRP的差异最为显著，g = -1.30（95% CI：-2.32 至 -0.29）；而hs-CRP（g = -0.70，95% CI：-1.01 至 -0.39）、IL-6（g = -0.51，95% CI：-0.80 至 -0.21）和TNF-α（g = -0.60，95% CI：-0.97 至 -0.24）则显示出中等程度但稳定且显著的影响。

据我们所知，这是首个汇总肥胖儿童炎症细胞因子数据的Meta分析。hs-CRP表现出中等程度的效应量，但结果更为稳定和可重复，这使其适用于临床应用。重要的是，当结合对青少年、成人和老年人的研究来看（在这些人群中，炎症细胞因子的动态变化与亚临床血管改变、心血管事件和死亡率相关），本研究发现具有额外的意义。儿童时期这些标志物水平的升高，可能作为长期心脏代谢风险的早期生物学信号。

1. Zhao X, Niu Y, Zhao XL, et al. Associations Between Serum TNF-α, IL-6, hs-CRP and GLMD in Obese Children and Adolescents: A Cross-Sectional Study. Diabetes Metab Syndr Obes. 2023;16:3915-3923. https://doi.org/10.2147/DMSO.S434482.

2. Dinov D, Khait A. Inflammatory markers in relation to pre-pubertal obesity. J Immunol. 2018;200(Supplement_1):106.3. https://doi.org/10.4049/jimmunol.200.Supp.106.3.

3. Selvaraju V, Babu JR, Geetha T. Association of salivary C-reactive protein with the obesity measures and markers in children. Diabetes Metab Syndr Obes Targets Ther. 2019;12:1239-1247. https://doi.org/10.2147/DMSO.S211624.

4. Yang SP, Gong CX, Cao BY, Yan C. [Relationship between serum high-sensitivity C-reactive protein and obesity and impaired glycose metabolism in children and adolescents]. Zhonghua Er Ke Za Zhi. 2006;44(12):933-936 (In Chinese).

5. Mărginean CO, Meliţ LE, Huțanu A, Ghiga DV, Săsăran MO. The adipokines and inflammatory status in the era of pediatric obesity. Cytokine. 2020;126:154925. https://doi.org/10.1016/j.cyto.2019.154925.

6. Engin A. The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation. In: Engin AB, Engin A, eds. Obesity and Lipotoxicity. Vol 960. Advances in Experimental Medicine and Biology. Springer International Publishing. 2017:221-245. https://doi.org/10.1007/978-3-319-48382-5_9.

7. Podeanu MA, Turcu-Stiolica A, Subțirelu MS, et al. C-Reactive Protein as a Marker of Inflammation in Children and Adolescents with Metabolic Syndrome: A Systematic Review and Meta-Analysis. Biomedicines. 2023;11(11):2961. https://doi.org/10.3390/biomedicines11112961.

8. Bizjak DA, Ammerpohl O, Schulz SVw, Wendt J, Steinacker JM, Flechtner-Mors M. Pro-inflammatory and (Epi-)genetic markers in saliva for disease risk in childhood obesity. Nutr Metab Cardiovasc Dis. 2022;32(6):1502-1510. https://doi.org/10.1016/j.numecd.2022.03.016.

9. Goehring KC, Marriage BJ, Oliver JS, Wilder JA, Barrett EG, Buck RH. Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2′-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial. J Nutr. 2016;146(12):2559-2566. https://doi.org/10.3945/jn.116.236919.

10. Gough A, Sitch A, Ferris E, Marshall T. Within-subject variation of C-reactive protein and high-sensitivity C-reactive protein: A systematic review and meta-analysis. PLOS ONE. 2024;19(11):e0304961. https://doi.org/10.1371/journal.pone.0304961.

11. Gul A, Yilmaz R. Determination of inflammation by TNF-alpha and IL-10 levels in obese children and adolescents. Nutr Hosp. 2024;41(4):788-792. https://doi.org/10.20960/nh.05064.

12. World Health Organization. Training Course on Child Growth Assessment. Geneva, WHO, 2008. ISBN 92 4 159507 8; ISBN 978 92 4 159507 0.

13. Cole TJ. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ. 2000;320(7244):1240. https://doi.org/10.1136/bmj.320.7244.1240.

14. Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat 11. 2002;(246):1-190.

15. Khadilkar VV, Khadilkar AV, Borade AB, Chiplonkar SA. Body mass index cut-offs for screening for childhood overweight and obesity in Indian children. Indian Pediatr. 2012;49(1):29-34. https://doi.org/10.1007/s13312-012-0011-y.

16. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14(1):135. https://doi.org/10.1186/1471-2288-14-135.

17. Gallardo-Gómez D, Richardson R, Dwan K. Standardized mean differences in meta-analysis: A tutorial. Cochrane Evid Synth Methods. 2024;2(3):e12047. https://doi.org/10.1002/cesm.12047.

18. Aleman MN, Luciardi MC, Albornoz ER, Bazán MC, Abregú AV. Relationship between inflammatory biomarkers and insulin resistance in excess-weight Latin children. Clin Exp Pediatr. 2024;67(1):37-45. https://doi.org/10.3345/cep.2022.01382.

19. Gokulakrishnan R, Delhikumar CG, Senthilkumar GP, Sahoo J, Kumar RR. Chronic Inflammatory Markers in Overweight and Obese Children: A Cross-sectional Analytical Study. Indian J Endocrinol Metab. 2024;28(5):542-547. https://doi.org/10.4103/ijem.ijem_353_23.

20. Kassem E, Na’amnih W, Shapira M, Ornoy A, Muhsen K. Comparison between School-Age Children with and without Obesity in Nutritional and Inflammation Biomarkers. J Clin Med. 2022;11(23):6973. https://doi.org/10.3390/jcm11236973.

21. Cura–Esquivel I, Perales-Quintana MM, Torres-González L, Guzmán-Avilán K, MuñozEspinosa L, Cordero-Pérez P. Metabolic, inflammatory and adipokine differences on overweight/obese children with and without metabolic syndrome: A cross-sectional study. PLOS ONE. 2023;18(3):e0281381. https://doi.org/10.1371/journal.pone.0281381.

22. Skvortsova OV, Migacheva NB, Mikhaylova EG. Biomarkers of chronic inflammation in children with obesity and their association with complications of the disease. Russ Pediatr J. 2025;28(1):47-53. https://doi.org/10.46563/1560-9561-2025-28-1-47-53.

23. Lang H, Loudermilk EN, Clark WA, et al. Inflammatory markers and body mass index amoung hispanic children. PLOS ONE. 2024;19(6):e0289523. https://doi.org/10.1371/journal.pone.0289523.

24. Podeanu MA, Vintilescu Ștefănița B, Sandu RE, et al. Ferritin as an Inflammatory Marker in Pediatric Metabolic Syndrome: Links to Obesity and Liver Ultrasound Alterations. Int J Mol Sci. 2025;26(8):3793. https://doi.org/10.3390/ijms26083793.

25. Mărginean CO, Meliţ LE, Ghiga DV, Mărginean MO. Early Inflammatory Status Related to Pediatric Obesity. Front Pediatr. 2019;7:241. https://doi.org/10.3389/fped.2019.00241.

26. Fernández-Vallejo B, Monteagudo FJ, Romero L, Aznárez MIL, Cobas MDCR, Pérez-Martínez L. Cross-Sectional Analysis of IL-6, TNF-α, Adiponectin, Leptin, and Klotho Serum Levels in Relation to BMI Among Overweight and Obese Children Aged 10–14 in La Rioja, Spain. Children. 2025;12(1):89. https://doi.org/10.3390/children12010089.

27. Giordano P, Del Vecchio GC, Cecinati V, et al. Metabolic, inflammatory, endothelial and haemostatic markers in a group of Italian obese children and adolescents. Eur J Pediatr. 2011;170(7):845-850. https://doi.org/10.1007/s00431-010-1356-7.

28. Chavira-Suárez E, Rosel-Pech C, Polo-Oteyza E, et al. Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR). PLOS ONE. 2020;15(8):e0237917. https://doi.org/10.1371/journal.pone.0237917.

29. Yasin J, Sharma C, Hashim MJ, Al Hamed S, AlKaabi J, Aburawi EH. Cross-Sectional Association Between Body Fat Composition and Biomarkers of Inflammation and Endothelial Dysfunction in Children with Overweight/Obesity. Diabetes Metab Syndr Obes. 2023;16:483-493. https://doi.org/10.2147/DMSO.S390071.

30. Christaki EV, Pervanidou P, Papassotiriou I, et al. Stress, Inflammation and Metabolic Biomarkers Are Associated with Body Composition Measures in Lean, Overweight, and Obese Children and Adolescents. Children. 2022;9(2):291. https://doi.org/10.3390/children9020291.

31. Simoes E, Correia-Lima J, Sardas L, et al. Sex dimorphism in inflammatory response to obesity in childhood. Int J Obes. 2021;45(4):879-887. https://doi.org/10.1038/s41366-021-00753-1.

32. Wolters M, Foraita R, Moreno LA, et al. Longitudinal associations between vitamin D status and biomarkers of inflammation in a pan-European cohort of children and adolescents. Eur J Nutr. 2024;63(8):3047-3060. https://doi.org/10.1007/s00394-024-03488-7.

33. Tam CS, Garnett SP, Cowell CT, et al. IL-6, IL-8 and IL-10 Levels in Healthy Weight and Overweight Children. Horm Res Paediatr. 2010;73(2):128-134. https://doi.org/10.1159/000277632.

34. Lund MAV, Thostrup AH, Frithioff-Bøjsøe C, et al. Low-grade inflammation independently associates with cardiometabolic risk in children with overweight/obesity. Nutr Metab Cardiovasc Dis. 2020;30(9):1544-1553. https://doi.org/10.1016/j.numecd.2020.04.024.

35. Chang CJ, Jian DY, Lin MW, Zhao JZ, Ho LT, Juan CC. Evidence in Obese Children: Contribution of Hyperlipidemia, Obesity-Inflammation, and Insulin Sensitivity. PLOS ONE. 2015;10(5):e0125935. https://doi.org/10.1371/journal.pone.0125935.

36. Juliaty A, Kurniasih D. Inflammatory markers and lipid profiles in obese children. Paediatr Indones. 2021;61(5):271-276. https://doi.org/10.14238/pi61.5.2021.271-6.

37. Maffeis L, Agostoni CV, Marafon DP, et al. Cytokines Profile and Lung Function in Children with Obesity and Asthma: A Case Control Study. Children. 2022;9(10):1462. https://doi.org/10.3390/children9101462.

38. Choi J, Joseph L, Pilote L. Obesity and C-reactive protein in various populations: a systematic review and meta-analysis. Obes Rev. 2013;14(3):232-244. https://doi.org/10.1111/obr.12003.

39. Zhao Y, Lv G. Correlation of C-reactive protein level and obesity in Chinese adults and children: a meta-analysis. J Endocrinol Invest. 2013;36(8):642-647. https://doi.org/10.3275/9004.

40. Dragoumani K, Troumbis A, Bacopoulou F, Chrousos G. Childhood and Adolescent Obesity with Somatic Indicators of Stress, Inflammation, and Dysmetabolism before and after Intervention: A Meta-Analysis. J Pers Med. 2023;13(9):1322. https://doi.org/10.3390/jpm13091322.

41. Bujtor M, Turner A, Torres S, Esteban-Gonzalo L, Pariante C, Borsini A. Associations of Dietary Intake on Biological Markers of Inflammation in Children and Adolescents: A Systematic Review. Nutrients. 2021;13(2):356. https://doi.org/10.3390/nu13020356.

42. Berton PF, Gambero A. Hepcidin and inflammation associated with iron deficiency in childhood obesity – A systematic review. J Pediatr (Rio J). 2024;100(2):124-131. https://doi.org/10.1016/j.jped.2023.06.002.

43. Skinner AC, Steiner MJ, Henderson FW, Perrin EM. Multiple Markers of Inflammation and Weight Status: Cross-sectional Analyses Throughout Childhood. Pediatrics. 2010;125(4):e801-e809. https://doi.org/10.1542/peds.2009-2182.

44. Tam CS, Clément K, Baur LA, Tordjman J. Obesity and low-grade inflammation: a paediatric perspective. Obes Rev. 2010;11(2):118-126. https://doi.org/10.1111/j.1467-789X.2009.00674.x.

45. Zatterale F, Longo M, Naderi J, et al. Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes. Front Physiol. 2020;10:1607. https://doi.org/10.3389/fphys.2019.01607.

46. Khanna D, Khanna S, Khanna P, Kahar P, Patel BM. Obesity: A Chronic Low-Grade Inflammation and Its Markers. Cureus. 2022;14(2):e22711. https://doi.org/10.7759/cureus.22711.

47. Gasmi A, Noor S, Menzel A, Doşa A, Pivina L, Bjørklund G. Obesity and Insulin Resistance: Associations with Chronic Inflammation, Genetic and Epigenetic Factors. Curr Med Chem. 2021;28(4):800-826. https://doi.org/10.2174/0929867327666200824112056.

48. Weijie Z, Meng Z, Chunxiao W, et al. Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer’s disease. Ageing Res Rev. 2024;99:102402. https://doi.org/10.1016/j.arr.2024.102402.

49. Rowicka G, Dyląg H, Chełchowska M, Weker H, Ambroszkiewicz J. Serum Calprotectin and Chemerin Concentrations as Markers of Low-Grade Inflammation in Prepubertal Children with Obesity. Int J Environ Res Public Health. 2020;17(20):7575. https://doi.org/10.3390/ijerph17207575.

50. Agbaje AO, Barmi S, Sansum KM, Baynard T, Barker AR, Tuomainen TP. Temporal causal longitudinal associations of high-sensitivity C-reactive protein with carotid intima-media thickness progression in adolescents: the ALSPAC birth cohort study. Eur Heart J. 2022;43(Supplement_2):ehac544.2246. https://doi.org/10.1093/eurheartj/ehac544.2246.

51. Tragomalou A, Paltoglou G, Manou M, et al. Non-Traditional Cardiovascular Risk Factors in Adolescents with Obesity and Metabolic Syndrome May Predict Future Cardiovascular Disease. Nutrients. 2023;15(20):4342. https://doi.org/10.3390/nu15204342.

52. Choi EJ, Lee HA, Park B, et al. Trajectory patterns for continuous metabolic syndrome score in childhood and the cardiovascular risk in adolescence. Sci Rep. 2021;11(1):22564. https://doi.org/10.1038/s41598-021-01566-y.

53. Posadas-Sánchez R, López-Uribe ÁR, Reyes-Barrera J, Ramírez-Bello J, Martínez-Alvarado MDR, Vargas-Alarcón G. Increased carotid intima-media thickness and cardiometabolic risk factors are associated with IL-6 gene polymorphisms in Mexican individuals: The Genetics of Atherosclerotic Disease Mexican study. Biomol Biomed. 2024;24(2):315-322. https://doi.org/10.17305/bb.2023.9495.

54. Palhares HMDC, Da Silva AP, Tomé JM, et al. Alterations in the inflammatory markers of the Tumor Necrosis Factor system in overweight and obese children and adolescents. PLOS One. 2025;20(5):e0319832. https://doi.org/10.1371/journal.pone.0319832.

55. Carrero JJ, Andersson Franko M, Obergfell A, Gabrielsen A, Jernberg T. hsCRP Level and the Risk of Death or Recurrent Cardiovascular Events in Patients With Myocardial Infarction: a Healthcare-Based Study. J Am Heart Assoc. 2019;8(11):e012638. https://doi.org/10.1161/JAHA.119.012638.

56. Mani P, Puri R, Schwartz GG, et al. Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome: A Secondary Analysis of the VISTA-16 Trial. JAMA Cardiol. 2019;4(4):314. https://doi.org/10.1001/jamacardio.2019.0179.

57. Katamine M, Minami Y, Nagata T, et al. High-sensitivity C-reactive protein, plaque vulnerability and adverse events in patients with stable coronary disease: An optical coherence tomography study. Int J Cardiol. 2025;421:132924. https://doi.org/10.1016/j.ijcard.2024.132924.

58. Opotowsky AR, Valente AM, Alshawabkeh L, et al. Prospective cohort study of C-reactive protein as a predictor of clinical events in adults with congenital heart disease: results of the Boston adult congenital heart disease biobank. Eur Heart J. 2018;39(34):3253-3261. https://doi.org/10.1093/eurheartj/ehy362.

59. Held C, White HD, Stewart RAH, et al. Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial. J Am Heart Assoc. 2017;6(10):e005077. https://doi.org/10.1161/JAHA.116.005077.

60. Batra G, Ghukasyan Lakic T, Lindbäck J, et al. Interleukin 6 and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Chronic Coronary Syndrome. JAMA Cardiol. 2021;6(12):1440. https://doi.org/10.1001/jamacardio.2021.3079.

61. Jia X, Buckley L, Sun C, et al. Association of interleukin-6 and interleukin-18 with cardiovascular disease in older adults: Atherosclerosis Risk in Communities study. Eur J Prev Cardiol. 2023;30(16):1731-1740. https://doi.org/10.1093/eurjpc/zwad197.

62. Ridker PM, Rifai N, Pfeffer M, Sacks F, Lepage S, Braunwald E. Elevation of Tumor Necrosis Factor-α and Increased Risk of Recurrent Coronary Events After Myocardial Infarction. Circulation. 2000;101(18):2149-2153. https://doi.org/10.1161/01.CIR.101.18.2149.

63. Cui G, Wang H, Li R, et al. Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke. J Neuroinflammation. 2012;9(1):235. https://doi.org/10.1186/1742-2094-9-235.

64. Morange PE, Tregouet DA, Godefroy T, et al. Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study. J Mol Med. 2008;86(10):1153-1161. https://doi.org/10.1007/s00109-008-0375-6.

65. Liu Y, Zhang C, Jiang L, et al. Relationship Between High-Sensitivity C-Reactive Protein and Long-Term Outcomes in Elderly Patients With 3-Vessel Disease. Angiology. 2022;73(1):60-67. https://doi.org/10.1177/00033197211021195.

66. Li ZH, Zhong WF, Lv YB, et al. Associations of plasma high-sensitivity C-reactive protein concentrations with all-cause and cause-specific mortality among middle-aged and elderly individuals. Immun Ageing. 2019;16(1):28. https://doi.org/10.1186/s12979-019-0168-5.

67. Kuoppamäki M, Salminen M, Vahlberg T, Irjala K, Kivelä SL, Räihä I. High sensitive C-reactive protein (hsCRP), cardiovascular events and mortality in the aged: A prospective 9-year follow-up study. Arch Gerontol Geriatr. 2015;60(1):112-117. https://doi.org/10.1016/j.archger.2014.10.002.

68. Li H, Liu W, Xie J. Circulating interleukin-6 levels and cardiovascular and all-cause mortality in the elderly population: A meta-analysis. Arch Gerontol Geriatr. 2017;73:257-262. https://doi.org/10.1016/j.archger.2017.08.007.

69. Bruunsgaard H, Andersen-Ranberg K, Hjelmborg J v.B, Pedersen BK, Jeune B. Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am J Med. 2003;115(4):278-283. https://doi.org/10.1016/s0002-9343(03)00329-2.