切换至 "中华医学电子期刊资源库"
高级检索
中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2022, Vol. 16 ›› Issue (01) : 25 -32. doi: 10.3877/cma.j.issn.1674-1358.2022.01.004

论著

肺炎支原体肺炎患儿支气管肺泡灌洗液白细胞介素-4、白细胞介素-6、干扰素-γ水平与病情和肺功能的关系
刘怀彬1, 张振坤,1, 闵婕1   
  1. 1. 221000　徐州市，徐州医科大学附属徐州市儿童医院呼吸科
  • 收稿日期:2021-04-12 出版日期:2022-02-15
  • 通信作者: 张振坤
  • 基金资助:
    江苏省妇幼保健协会科研项目(No. FYX201912)

Relationships between interleukin-4, interleukin-6, interferon-γ levels of bronchoalveolar lavage fluid and disease condition and pulmonary function of children with Mycoplasma pneumonia pneumonia

Huaibin Liu1, Zhenkun Zhang,1, Jie Min1   

  1. 1. Respiratory Department, Xuzhou Children’s Hospital Affiliated to Xuzhou Medical University, Xuzhou 221000, China
  • Received:2021-04-12 Published:2022-02-15
  • Corresponding author: Zhenkun Zhang
全文 ( 12 ) 下载PDF ( 2 ) 导出引用
引用本文：

刘怀彬, 张振坤, 闵婕. 肺炎支原体肺炎患儿支气管肺泡灌洗液白细胞介素-4、白细胞介素-6、干扰素-γ水平与病情和肺功能的关系[J/OL]. 中华实验和临床感染病杂志(电子版), 2022, 16(01): 25-32.

Huaibin Liu, Zhenkun Zhang, Jie Min. Relationships between interleukin-4, interleukin-6, interferon-γ levels of bronchoalveolar lavage fluid and disease condition and pulmonary function of children with Mycoplasma pneumonia pneumonia[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(01): 25-32.

目的

分析肺炎支原体肺炎（MPP）患儿支气管肺泡灌洗液（BALF）中白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、干扰素-γ（IFN-γ）水平与病情和肺功能的关系。

方法

选取徐州市儿童医院2019年5月至2020年10月收治的109例MPP患儿（研究组）和102例急性支气管异物患儿（对照组），均实施支气管肺泡灌洗术。研究组MPP患儿根据病情分为轻症组（85例）和重症组（24例），并根据患儿肺功能损伤程度分为肺功能正常组（26例）、轻度损伤组（32例）、中度损伤组（30例）和重度损伤组（21例）。取入组患儿BALF，采用酶联免疫吸附试验（ELISA）检测IL-4、IL-6、IFN-γ水平并进行比较；比较研究组不同病情、不同肺功能损伤患儿BALF中IL-4、IL-6和IFN-γ水平：两组间比较采用成组设计资料t检验；多组间整体比较采用方差分析后组间两两比较采用LSD-t检验。应用Pearson相关分析研究组患儿BALF中IL-4、IL-6、IFN-γ水平与肺功能的关系。

结果

研究组患儿BALF中IL-4、IL-6、IFN-γ水平均高于对照组[IL-4：（142.4 ± 24.7）pg/ml vs.（73.2 ± 13.0）pg/ml，t = 25.159、P < 0.001；IL-6：（56.4 ± 10.3）pg/ml vs.（11.2 ± 2.3）pg/ml，t = 43.399、P < 0.001；IFN-γ：（90.2 ± 16.3）pg/ml vs.（41.8 ± 6.8）pg/ml，t = 27.857、P < 0.001]。研究组中重症组患儿BALF中IL-4、IL-6、IFN-γ水平分别为（200.7 ± 36.7）pg/ml、（103.3 ± 16.8）pg/ml和（113.5 ± 21.9）pg/ml，均显著高于轻症组[（125.9 ± 22.4）pg/ml、（43.1 ± 7.8）pg/ml和（83.6 ± 14.1）pg/ml]（IL-4：t = 12.378、P < 0.001，IL-6：t = 25.010、P < 0.001，IFN-γ：t = 8.035、P < 0.001），差异有统计学意义。研究组中肺功能正常组患儿BALF中IL-4、IL-6和IFN-γ水平分别为（81.6 ± 15.5）pg/ml、（20.4 ± 4.2）pg/ml和（74.7 ± 11.9）pg/ml，轻度损伤者分别为（102.5 ± 19.9）pg/ml、（48.9 ± 8.2）pg/ml和（89.2 ± 11.1）pg/ml，中度损伤者分别为（145.7 ± 25.2）pg/ml、（60.2 ± 10.2）pg/ml和（95.4 ± 12.8）pg/ml，重度损伤者分别为（273.7 ± 42.1）pg/ml、（106.9 ± 17.6）pg/ml和（103.2 ± 13.2）pg/ml。肺功能轻度、中度、重度损伤组患儿BALF中IL-4、IL-6和IFN-γ水平均高于肺功能正常组（P均< 0.05），肺功能中度、重度损伤组患儿以上指标水平均高于肺功能轻度损伤组（P均< 0.05），肺功能重度损伤患儿均高于肺功能中度损伤者（IL-4：t = 13.581、P < 0.001，IL-6：t = 11.956、P < 0.001，IFN-γ：t = 2.117、P = 0.039），差异均有统计学意义。研究组患儿BALF中IL-4、IL-6、IFN-γ水平与1秒用力呼气容积（FEV1）、用力肺活量（FVC）、呼气流量峰值（PEF）均呈负相关（IL-4与FEV1、FEV1/FVC、PEF相关性：r =-0.834、P = 0.025，r =-0.810、P = 0.009，r =-0.901、P = 0.002；IL-6与FEV1、FEV1/FVC、PEF：r =-0.816、P = 0.003，r =-0.795、P = 0.012，r =-0.743、P = 0.007；IFN-γ与FEV1、FEV1/FVC、PEF：r =-0.756、P = 0.012，r =-0.738、P = 0.010，r =-0.725、P = 0.017）。

结论

MPP患儿BALF中IL-4、IL-6和IFN-γ水平均偏高，且3个指标水平与病情、肺功能均有关。

关键词: 肺炎支原体肺炎, 支气管肺泡灌洗液, 白细胞介素-4, 白细胞介素-6, 干扰素-γ
Objective

To investigate the relationships between the levels of interleukin-4 (IL-4), interleukin-6 (IL-6) and interferon-γ (IFN-γ) of bronchoalveolar lavage fluid (BALF) and the disease condition and pulmonary function in children with Mycoplasma pneumoniae pneumonia (MPP).

Methods

Total of 109 cases with MPP (study group) and 102 cases of acute bronchial foreign bodies (control group) in Xuzhou Children’s Hospital Affiliated to Xuzhou Medical University from May 2019 to October 2020 were enrolled. The patients in study group were divided into mild disease group (85 cases) and severe disease group (24 cases) according to the conditions; and divided into normal lung function group (26 cases), mild lung function injury group (32 cases), moderate lung function injury group (30 cases) and severe lung function injury group (21 cases) according to the degree of lung function injury. The levels of IL-4, IL-6 and IFN-γ of BALF among all cases were detected by enzyme-linked immunosorbent assay (ELISA). The levels of IL-4, IL-6 and IFN-γ of BALF were compared among cases with different conditions and different grades of lung function injury. The above indexes were compared between two groups by t-test for group design data; multi-group overall comparison were taked by ANOVA, and pairwise comparison were analyzed by LSD-t test. The correlations between the levels of IL-4, IL-6, IFN-γ of BALF and lung function were analyzed by Pearson correlation-analysis.

Results

The levels of IL-4, IL-6 and IFN-γ of BALF of cases in study group were significantly higher than those of control group [IL-4: (142.4 ± 24.7) pg/ml vs. (73.2 ± 13.0) pg/ml: t = 25.159, P < 0.001; IL-6: (56.4 ± 10.3) pg/ml vs. (11.2 ± 2.3) pg/ml: t = 43.399, P < 0.001; IFN-γ: (90.2 ± 16.3) pg/ml vs. (41.8 ± 6.8) pg/ml: t = 27.857, P < 0.001]. The levels of IL-4, IL-6 and IFN-γ of BALF of children in severe injury group were (200.7 ± 36.7) pg/ml, (103.3 ± 16.8) pg/ml and (113.5 ± 21.9) pg/ml, which were significantly higher than those of mild disease group [(125.9 ± 22.4) pg/ml, (43.1 ± 7.8) pg/ml and (83.6 ±14.1) pg/ml], with significant difference (t = 12.378, P < 0.001; t = 25.010, P < 0.001; t = 8.035, P < 0.001). The levels of IL-4, IL-6 and IFN-γ of BALF in children with normal lung function were (81.6 ± 15.5) pg/ml, (20.4 ± 4.2) pg/ml, (74.7 ± 11.9) pg/ml, and (102.5 ± 19.9) pg/ml, (48.9 ± 8.2) pg/ml, (89.2 ± 11.1) pg/ml in mild lung function injury group, and (145.7 ± 25.2) pg/ml, (60.2 ± 10.2) pg/ml, (95.4 ± 12.8) pg/ml in moderate lung function injury group, and (273.7 ± 42.1) pg/ml, (106.9 ± 17.6) pg/ml, (103.2 ± 13.2) pg/ml in severe lung function injury group, respectively. The levels of IL-4, IL-6 and IFN-γ in BALF of cases in mild, moderate and severe lung injury groups were significantly higher than those of normal lung function group (all P < 0.05), the levels of the above three indexes of cases in moderate, severe lung injury function group were significantly higher than those of mild lung injury group (all P < 0.05), and those of severe lung injury group were significantly higher than those of moderate lung injury group (IL-4: t = 13.581, P < 0.001; IL-6: t = 11.956, P < 0.001; IFN-γ: t = 2.117, P = 0.039), all with significant differences. The levels of IL-4, IL-6 and IFN-γ of BALF in study group were negatively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) (IL-4 with FEV1, FEV1/FVC and PEF: r =-0.834, P = 0.025; r =-0.810, P = 0.009; r =-0.901, P = 0.002; IL-6 with FEV1, FEV1/FVC and PEF: r =-0.816, P = 0.003; r =-0.795, P = 0.012; r =-0.743, P = 0.007; IFN-γ with FEV1, FEV1/FVC and PEF: r =-0.756, P = 0.012; r =-0.738, P = 0.010; r =-0.725, P = 0.017).

Conclusions

The levels of IL-4, IL-6 and IFN-γ of BALF were increased in children with MPP, which were correlated with the disease conditions and lung function.

Key words: Mycoplasma pneumoniae pneumonia, Bronchoalveolar lavage fluid, Interleukin-4, Interleukin-6, Interferon-γ
表1 研究组与对照组患儿BALF中IL-4、IL-6和IFN-γ水平（± s，pg/ml）
组别 例数 IL-4 IL-6 IFN-γ
研究组 109 142.4 ± 24.7 56.4 ± 10.3 90.2 ± 16.3
对照组 102 73.2 ± 13.0 11.2 ± 2.3 41.8 ± 6.8
t值   25.195 43.399 27.857
P值   < 0.001 < 0.001 < 0.001
表2 研究组不同病情患儿BALF中IL-4、IL-6和IFN-γ水平（± s，pg/ml）
组别 例数 IL-4 IL-6 IFN-γ
轻症组 85 125.9 ± 22.4 43.1 ± 7.8 83.6 ± 14.1
重症组 24 200.7 ± 36.7 103.3 ± 16.8 113.5 ± 21.9
t值   12.378 25.010 8.035
P值   < 0.001 < 0.001 < 0.001
表3 研究组不同肺功能分级患儿BALF中IL-4、IL-6和IFN-γ水平（± s，pg/ml）
组别 例数 IL-4 IL-6 IFN-γ
正常组 26 81.6 ± 15.5 20.4 ± 4.2 74.7 ± 11.9
轻度损伤组 32 102.5 ± 19.9 48.9 ± 8.2 89.2 ± 11.1
中度损伤组 30 145.7 ± 25.2 60.2 ± 10.2 95.4 ± 12.8
重度损伤组 21 273.7 ± 42.1 106.9 ± 17.6 103.2 ± 13.2
F值   247.644 267.482 14.075
P值   < 0.001 < 0.001 < 0.001
图1 研究组患儿BALF中IL-4水平与FEV1、FEV1/FVC和PEF的相关性注：A：BALF中IL-4水平与FEV1相关性；B：BALF中IL-4水平与FEV1/FVC相关性；C：BALF中IL-4水平与PEF相关性
图2 研究组患儿BALF中IL-6水平与FEV1、FEV1/FVC和PEF的相关性注：A：BALF中IL-6水平与FEV1相关性；B：BALF中IL-6水平与FEV1/FVC相关性；C：BALF中IL-6水平与PEF相关性
图3 研究组患儿BALF中IFN-γ水平与FEV1、FEV1/FVC和PEF的相关性注：A：BALF中IFN-γ水平与FEV1相关性；B：BALF中IFN-γ水平与FEV1/FVC相关性；C：BALF中IFN-γ水平与PEF相关性
[1]
陈晨，黄旭强，赵丹洋, 等. 2014-2018年患儿肺炎支原体耐药调查分析[J]. 中华医院感染学杂志,2019,29(12):1850-1855.
[2]
Poddighe D, Comi EV, Brambilla I, et al. Increased total serum immunoglobulin E in children developing Mycoplasma pneumoniae-related extra-pulmonary diseases[J]. Iran J Allergy Asthma Immunol,2018,17(5):490-496.
[3]
Tian F, Chen LP, Yuan G, et al. Differences of TNF-α, IL-6 and Gal-3 in lobar pneumonia and bronchial pneumonia caused by mycoplasma pneumoniae[J]. Technol Health Care,2020,28(6):711-719.
[4]
Wu P, Wang J. Changes and significance of serum sB7-H3 and cytokines in children with Mycoplasma pneumonae pneumonia[J]. J Coll Physicians Surg Pak,2020,30(3):268-271.
[5]
巫伟生，李斯，张必旗, 等. 肺炎支原体感染不同病期婴幼儿免疫功能及炎症因子的动态变化[J/CD]. 中华实验和临床感染病杂志(电子版),2019,13(1):54-59.
[6]
Li G, Fan L, Wang Y, et al. High co-expression of TNF-α and CARDS toxin is a good predictor for refractory Mycoplasma pneumoniae pneumonia[J]. Mol Med,2019,25(1):38.
[7]
Maselli DJ, Medina JL, Brooks EG, et al. The immunopathologic effects of Mycoplasma pneumoniae and community-acquired respiratory distress syndrome toxin. A primate model[J]. Am J Respir Cell Mol Biol,2018,58(2):253-260.
[8]
Li QL, Wu YY, Sun HM, et al. The role of miR-29c/B7-H3/Th17 axis in children with Mycoplasma pneumoniae pneumonia[J]. Ital J Pediatr,2019,45(1):61.
[9]
赵茜叶，侍苏杰，徐海燕, 等. 肺炎支原体肺炎患儿肺功能变化与慢性咳嗽的相关性[J]. 中华实用儿科临床杂志,2019,34(4):270-273.
[10]
中华医学会儿科学分会呼吸学组，《中华实用儿科临床杂志》编辑委员会. 儿童肺炎支原体肺炎诊治专家共识2015年版[J]. 中华实用儿科临床杂志,2015,30(17):1304-1308.
[11]
江载芳，申昆玲，沈颖, 等. 诸福棠实用儿科学[M]. 8版. 北京: 人民卫生出版社,2015:1282-1284.
[12]
Wang X, Zhong LJ, Chen ZM, et al. Necrotizing pneumonia caused by refractory Mycoplasma pneumonia pneumonia in children[J]. World J Pediatr,2018,14(4):344-349.
[13]
Rodman Berlot J, Krivec U, Praprotnik M, et al. Clinical characteristics of infections caused by Mycoplasma pneumoniae P1 genotypes in children[J]. Eur J Clin Microbiol Infect Dis,2018,37(7):1265-1272.
[14]
文福生，张必旗，常佳军. 多指标联合检测在小儿细菌性肺炎病原学诊断中的应用[J/CD]. 中华实验和临床感染病杂志(电子版),2020,14(5):72-77.
[15]
Ye Q, Mao JH, Shu Q, et al. Mycoplasma pneumoniae induces allergy by producing P1-specific immunoglobulin E[J]. Ann Allergy Asthma Immunol,2018,121(1):90-97.
[16]
刘芳君，龚财惠，秦江蛟, 等. 肺炎支原体肺炎婴幼儿肺功能的变化[J]. 中国当代儿科杂志,2020,22(2):118-123.
[17]
Smith-Norowitz TA, Weaver D, Norowitz YM, et al. Doxycycline suppresses Chlamydia pneumoniae induced interferon-gamma responses in peripheral blood mononuclear cells in children with allergic asthma[J]. J Infect Chemother,2018,24(6):470-475.
[18]
Totten AH, Xiao L, Luo D, et al. Allergic airway sensitization impairs antibacterial IgG antibody responses during bacterial respiratory tract infections[J]. J Allergy Clin Immunol,2019,143(3):1183-1197.
[19]
李俊梅，郑成中，张曼, 等. 儿童难治性肺炎支原体肺炎的临床特点及血清IL-4, IL-6, IL-10, IFN-γ的变化分析[J]. 现代生物医学进展,2018,18(24):178-182.
[20]
张同强，徐勇胜，林书祥, 等. 支原体肺炎患儿血清及支气管肺泡灌洗液IL-2, IL-4和IL-6的检测及意义[J]. 广东医学,2018,39(20):3055-3057.
[21]
Wang X, Zhong LJ, Chen ZM, et al. Necrotizing pneumonia caused by refractory Mycoplasma pneumonia pneumonia in children[J]. World J Pediatr,2018,14(4):344-349.
[22]
Dai W, Wang H, Zhou Q, et al. The concordance between upper and lower respiratory microbiota in children with Mycoplasma pneumoniae pneumonia[J]. Emerg Microbes Infect,2018,7(1):92.
[23]
Kuang Z, Bennett RC, Lin J, et al. Surfactant phospholipids act as molecular switches for premature induction of quorum sensing-dependent virulence in Pseudomonas aeruginosa[J]. Virulence, 2020,11(1):1090-1107.
[24]
Liu M, Li H, Xue CX, et al. Differences in inflammatory marker patterns for adult community-acquired pneumonia patients induced by different pathogens[J]. Clin Respir J,2018,12(3):974-985.
[25]
Meyer Sauteur PM, Theiler M, Buettcher M, et al. Frequency and clinical presentation of mucocutaneous disease due to mycoplasma pneumoniae infection in children with community-acquired pneumonia[J]. JAMA Dermatol,2020,156(2):144-150.
[26]
郑茂，陈瑶，符佳. 难治性肺炎支原体肺炎患儿的早期临床特征及相关细胞因子水平变化[J]. 中国医药,2017,10(12):1499-1502.
[27]
谢晓虹，王崇杰，张光莉, 等. 肺炎支原体肺炎患儿支气管肺泡灌洗液细胞因子特点及相关性分析[J]. 临床儿科杂志,2020,38(12):10-16.
[28]
Chaudhry SR, Kahlert UD, Kinfe TM, et al. Elevated systemic IL-10 levels indicate immunodepression leading to nosocomial infections after aneurysmal subarachnoid hemorrhage (SAH) in patients[J]. Int J Mol Sci,2020,21(5):1569.
[29]
周云，陈丽蓥，冉扬, 等. 小儿细菌性肺炎和支原体肺炎实验室炎性指标分析[J]. 儿科药学杂志,2019,25(3):4-6.
[1] 薛嘉怡, 王丽, 艾涛. 巨噬细胞在儿童肺炎支原体肺炎中作用机制的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2023, 19(06): 643-648.
[2] 郑宝英, 黄小兰, 贾楠, 朱春梅. 儿童难治性肺炎支原体肺炎早期预警指标[J/OL]. 中华实验和临床感染病杂志(电子版), 2024, 18(04): 215-221.
[3] 杨梅, 周春, 赵艾红, 王琴. 儿童难治性肺炎支原体肺炎所致塑型性支气管炎风险列线图模型的构建[J/OL]. 中华实验和临床感染病杂志(电子版), 2023, 17(04): 274-281.
[4] 董大红, 周明虎, 李芝朋, 许正峰. 碳青霉烯类抗生素联合呼吸机治疗肺部感染的临床疗效分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 793-796.
[5] 马甜甜, 张红军, 顾兴, 李文洁, 赵延军, 苟超伦, 严雯. 支气管镜在儿童重症肺炎支原体肺炎中的应用分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(03): 397-401.
[6] 李苑莹, 龚金如, 陈晓璇, 孙瑞琳. 成人肺炎支原体肺炎临床特征分析[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(02): 223-228.
[7] 朱丽臻, 范文萃, 李梦瑶, 李丽, 张月, 石艳红. 外周血NLRP3、IL-18和IL-1β在肺炎支原体肺炎患儿中的表达及检测意义[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(06): 860-863.
[8] 丁晓静, 张丹琦, 杨伟. 布地奈德雾化吸入联合金嗓开音胶囊治疗小儿急性喉炎的疗效及对IFN-γ、SAA、IL-6的影响[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(03): 391-393.
[9] 彭博, 张奕, 朱春梅. 支气管肺泡灌洗液中Th1/Th2、IL-6水平与儿童肺炎支原体肺炎伴喘息的相关性分析[J/OL]. 中华肺部疾病杂志(电子版), 2023, 16(02): 212-214.
[10] 肖田恬, 丁桃容, 刘婷婷. 异丙托溴铵联合糖皮质激素治疗COPD的临床分析[J/OL]. 中华肺部疾病杂志(电子版), 2022, 15(06): 885-887.
[11] 刘一, 文旖旎, 吴映辉. 过敏性紫癜患儿外周血辅助性T细胞、调节性T细胞细胞因子与肾损害的相关性分析[J/OL]. 中华肾病研究电子杂志, 2023, 12(05): 271-275.
[12] 王永楠, 汤畅通, 殷杰, 谭溢涛. 微创钻孔引流术与神经内镜血肿清除术治疗临界量基底节脑出血的效果对比分析[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 286-292.
[13] 陈蕊, 杨洪娜, 方巍, 李鑫鑫, 李甜甜, 于孝义, 王艳雪, 李文玉. 血清与支气管肺泡灌洗液中细胞因子水平与肺内外ARDS的相关性研究[J/OL]. 中华重症医学电子杂志, 2023, 09(03): 251-258.
[14] 李润东, 豆小文, 张秀明. 失笑散联合胃复春治疗慢性萎缩性胃炎的疗效及对血清免疫受体和炎症因子水平的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 470-473.
[15] 牛红霞, 毛月然, 陈琦琪, 胥俊越, 董静, 王振, 杨彦娜, 张明. 可溶性程序性死亡受体-1及其配体和干扰素-γ在急性冠脉综合症患者血清中的表达特征和临床意义[J/OL]. 中华卫生应急电子杂志, 2024, 10(01): 10-15.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号