免疫治疗对毛细支气管炎后哮喘发生的干预机制研究

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (9): 1030-1034.

免疫治疗对毛细支气管炎后哮喘发生的干预机制研究

刘雅丽, 杨锡强¹

浙江省杭州市第一人民医院儿科, 杭州 310006, 浙江;
¹重庆医科大学附属儿童医院儿科研究所, 重庆 400014

收稿日期:2006-07-11 修回日期:2006-07-11 出版日期:2006-09-26 发布日期:2020-11-05
通讯作者: 杨锡强, 男, 博士生导师, 研究方向:儿童免疫学。Tel:023-63632756
作者简介:刘雅丽, 女, 副主任医师, 博士, 研究方向:小儿临床免疫。Tel:13136179862 E-mail:Wjyliu@163.com
基金资助:
卫生部科研基金项目(No98-1-353)

Effect of Bacille Calmette Guerin inoculation with or without IFN-γ/Vit A on immunologic status of infant with bronchiolitis

LIU Ya-li, YANG Xi-qiang¹

First Hospital of Hangzhoushi , Hangzhou 300016 , Zhejiang, China;
¹Children's Hospital , Chongqing University of Medical Sciences, Chongqing 400014 , China

Received:2006-07-11 Revised:2006-07-11 Online:2006-09-26 Published:2020-11-05

摘要/Abstract

摘要： 目的探讨卡介苗(Bacille Calmette Guerin ,BCG) 或联用干扰素γ(IFN-γ) /维生素A(VitA) 对毛细支气管炎患儿免疫功能状态的影响。方法毛细支气管炎患儿共44 例, 25 例患儿给予单独BCG 或合并IFN-γ/VitA 治疗, 治疗前和治疗3个月后分别进行纯结核蛋白衍生物(PPD) 皮试, 采用ELISA 和逆转录-聚合酶链反应(RT-PCR) 方法测定外周血单个核细胞(peripheral blood mononuclear cells, PBMC)体外产生IL-12 、IL-18 、IL-10 、IL-4 、IFN-γ的水平及膜表面蛋白质分子淋巴细胞活化基因3(lymphocyte activation gene-3, LAG-3) mRNA 的表达, 并随访平均1年时间, 临床观察喘息发作的情况。19 例未接受BCG 接种的毛细支气管炎患儿, 作为疾病对照组。结果干预后IL-12 、IL-18 、及IFN-γ水平明显高于干预前, LAG-3mRNA 的表达增强, IL-4 水平显著降低,差异具有显著意义, IL-10 水平略下降。BCG 接种后PPD 平均硬结直径大于干预前及毛细支气管炎对照组恢复期。BCG 单用或联用IFN-γ/(VitA) 组1 年内喘息发作频率低于对照组恢复期, 单用或联用组间差异无显著意义。临床疗效及细胞因子的产生在合并IFN-γ/VitA 治疗组未显示出优势。结论 BCG 可促进毛细支气管炎患儿PPD 皮试阳转、增强TH₁ 细胞功能的作用, 推测IL-10 水平未显著降低可能与BCG 诱导产生调节性T 细胞(CD₄ +CD₂₅ +Tr) 有关。

关键词: 毛细支气管炎, 卡介苗, PPD 反应, 辅助性T 细胞1/辅助性T 细胞2, 细胞因子

Abstract: AIM: To discuss the effects of Bacille Calmette Guerin (BCG) inoculation with or without supplement of vitamin A/IFN-γon tubercle bacillus protein purified derivative (PPD) skin test, wheezing episode and in vitro the cytokine levels of peripheral blood mononuclear cells (PBMC) in infants with acute bronchiolitis.METHODS: 44 acute bronchiolitis infants (ABI) were treated with BCG alone or BCG combined with Vitamin A/IFN-γ.19 ABI treated without BCG as control.PPD skin test, in vitro production of IL-10 、IL-12 、IL-18 、IL-4 and IFN-γby supernatant of PBMC of bronchiolitis measured by ELISA, and expression of lymphocyte activation gene-3 (LAG-3) mRNA from PBMC of bronchiolitis measured by semi-quantitative RT-PCR were observed before and 3 months after BCG inoculation.Follow upfor average 12 months was to observe thewheezing episodes.RESULTS: The diameters of PPD skin test in ABI after BCG inoculation combined with IFN-γ/VitA were larger than those of ABI before inoculation and control group.The frequencies and persistence of wheezing were lower in interfered infants with acute bronchiolitis either by BCG alone or BCG combined with IFN-γ/VitA than those of control groupby 1 year.IL-12 、IL-18 and IFN-γactivities in ABI treated with BCG or BCG combined with IFN-γ/Vitamin A in vitro were higher than those of pre-treatment bronchiolitis infants;the level of IL-4 was lower;the level of IL-10 was a little bit lower, and expression of LAG-3 mRNA was stronger.Frequency of wheezing episode in 1 year in acute bronchiolitis infants with BCG or BCG combined with IFN-γ/Vitamin A was lower than that of control group.There were no difference between ABIwith BCG or BCG combined with IFN-γ/Vitamin A.Clinical manifestation and the level of cytokines do not show superiority in BCG with IFN-γ/Vitamin A.CONCLUSION: BCG inoculation is able to enhance PPD skin test response,promote Th1 reactivity, and prevent from recurrent wheezing after acute bronchiolitis.The level of IL-10 was degraded lightly after BCG intervention, presumably concerning with regular T cells(CD4 +CD25 +Tr) induced by BCG inoculation.

Key words: bronchiolitis, Bacille Calmette Guerin, PPD skin test, TH1/TH2, cytokine

中图分类号:

R965.2
R966

刘雅丽, 杨锡强. 免疫治疗对毛细支气管炎后哮喘发生的干预机制研究[J]. 中国临床药理学与治疗学, 2006, 11(9): 1030-1034.

LIU Ya-li, YANG Xi-qiang<. Effect of Bacille Calmette Guerin inoculation with or without IFN-γ/Vit A on immunologic status of infant with bronchiolitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(9): 1030-1034.

参考文献

1 Martin MA.Respiratory syncytial virus infection and asthma[J].Allergol Immunopathol, 2001;29:140-6
2 Kim CK, Kim SW, Park CS, Kim BI, Kang H, Koh YY.Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis[J].J Allergy Clin Immunol, 2003;112:64-71
3 Annunziato F, Manetti R, Tomasevic I, Guidizi MG, Biagiotti R, Gianno V, et al.Expression and release of LAG-3-encoded protein by human CD4+T cells are associated with IFN-gamma production[J].FASEB J, 1996;10:769-76
4 Trefny P, Stricker T, Baerlocher C, Sennhauser FH.Family history of atopy and clinicl course of RSV infection in ambulatory and hospitalized infants[J].Pediatr Pulmonol, 2000;30:302-6
5 Shirakawa T, Enomoto T, Sasaki S, Taniguchi K, Motonaga M, Akahori W, et al.The inverse association between tuberculin responses and atopic disorder[J].Science, 1997;275:77-9
6 Koh YI, Choi IS, Kim WY.BCG infection in allergen-presensitized rats suppresses Th2 immune response and prevents the development of allergic asthmatic reaction[J].J Clin Immunol,2001;21:51-9
7 Horner AA, Van Uden JH, Zubeldia JM.DNA-based immunotherapeutics for the treatment of allergic disease[J].Immunol Rev, 2001;170:102-18
8 Choi IS, Koh YI.Therapeutic effects of BCG vaccination in adult asthmatic patients:a randomized, controlled trial[J].Ann Allergy Asthma Immunol, 2002;88:584-91
9 Choi IS, Koh YI.Effects of BCG revaccination on asthma.Al-lergy , 2003;58:1114-6
10 Choi IS, Koh YI.Therapeutic effects of BCG vaccination in adult asthmatic patients:arandomized controlled trial[J].Ann Allergy Asthma Immunol, 2002;88:584-91
11 Shirtcliffe PM, Easthope SE, ChengS, Weatherall M, Tan PL,LeGros G, et al.The effect of delipidated deglycolipidated (DDMV) and heat -killed Mycobacterium vaccae in asthma [J].Am J Respir Crit Care Med, 2001;163:1410-4
12 Wong GW, Hui DS, Tam CM, Chan HH, Fok TF, Chan-Yeung M, et al.Asthma, atopy and tuberculin responses in Chinese schoolchildren in Hong Kong[J].Thorax, 2001;56:770-3
13 刘恩梅, 罗嘉慧, 李秋, 杨锡强.比较卡介苗及其成分对脐血单核细胞转化树突状细胞成熟影响[J].临床儿科杂志, 2002;20:589-91
14 Youngil I, Koh Inseon S, Choi Je-Jung L.Effects of Cytokine Milieu Secreted by BCG-treated Dendritic Cells on Allergen-Specific Th Immune Response[J].J Korean Med Sci, 2004;19:640-6
15 Jeffrey AB, Abul KA.Natural versus adaptive regulatory T cells[J].Nat Rev Immunol, 2003;3:253-7
16 Taylor A, Verhagen J, Akdis CA, AkdisM.T regulatory cells in allergy and health:a question of allergen specificity and balance[J].Int Arch Allergy Immunol, 2004;135:73-82
17 Akbari O, Freeman GJ, Meyer EH.Antigen-specific regulatory T cells developvia the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity[J].NatMed, 2002;8:1024-32
18 Zuany-Amorim C, Sawicka E, Manlius C, Le Moine A, Brunet LR, Kemeny DM, et al.Suppression of airway eosinophilia by killedMycobacterium vaccae-induced allergen-specific regulatory T-cells[J].Nat Med, 2002;8:625-9

[1]	马怡彤, 马建红, 高亚婷, 刘畅. 脂肪细胞因子在子宫内膜癌中的作用及研究进展[J]. 中国临床药理学与治疗学, 2023, 28(11): 1315-1320.
[2]	张威, 王鸿渊, 雷晓航, 赵英帅, 吕炜超, 张建国. 中高危膀胱癌应用卡介苗+吡柔比星与卡介苗+吉西他滨预防术后复发的效果及对血清AGR、PON1的影响[J]. 中国临床药理学与治疗学, 2023, 28(10): 1146-1153.
[3]	黄好, 贾虹, 王晓霜, 张鹭, 蒋华. 负载MAGE-A3抗原的树突状细胞与细胞因子诱导杀伤细胞共培养对子宫内膜癌肿瘤干细胞及恶性进展的影响[J]. 中国临床药理学与治疗学, 2023, 28(1): 42-50.
[4]	何秀娟, 马慧可, 刘青武, 陈佳, 林燕, 李萍. 细胞因子在创面修复中的研究进展[J]. 中国临床药理学与治疗学, 2021, 26(5): 579-585.
[5]	吴加元，郑丽，莫娟芬，郭丽，曹晨曦，鲍轶. N-乙酰半胱氨酸调控非酒精性脂肪性肝病小鼠外周循环及肝脏局部髓源抑制细胞的研究[J]. 中国临床药理学与治疗学, 2019, 24(9): 989-996.
[6]	李敏，王珊珊，刘中和，姜德国. p38MAPK信号通路在慢性牙髓炎疼痛大鼠中的表达及作用机制研究[J]. 中国临床药理学与治疗学, 2019, 24(6): 644-649.
[7]	卜璋于，吴黎明，俞小虹，刘珏，邓琳. 柴胡解毒汤治疗尖锐湿疣的疗效观察和机制探讨[J]. 中国临床药理学与治疗学, 2019, 24(6): 681-686.
[8]	翟硕，李娜，陈蓓宁，寇俊萍，邢为藩，张评浒. 水飞蓟在治疗慢性肝炎中的研究进展[J]. 中国临床药理学与治疗学, 2019, 24(5): 573-579.
[9]	胡玉平，周海云，黄巧玲，姚轶敏. 丹皮酚对FSL-1与IL-4共刺激诱导树突状细胞成熟及细胞因子表达的影响[J]. 中国临床药理学与治疗学, 2019, 24(1): 14-19.
[10]	毛庆东. 重组人干扰素alfa2b氧驱雾化吸入佐治毛细支气管炎疗效及安全性观察[J]. 中国临床药理学与治疗学, 2018, 23(8): 927-931.
[11]	厉芳，郑浏璞，翁建龙，郭涛，宋兴伟，郑荣远. 咪唑克生减缓大鼠实验性自身免疫性脑脊髓炎脑损伤的保护作用时间窗研究[J]. 中国临床药理学与治疗学, 2018, 23(1): 1-7.
[12]	宋美情. 二甲双胍对2型糖尿病伴高血压患者骨密度及胰岛素抵抗、细胞因子的影响[J]. 中国临床药理学与治疗学, 2017, 22(6): 694-698.
[13]	茆红霞，金灵青，刘双春. 硫酸氨基葡萄糖联合参麦注射液治疗膝骨性关节炎的疗效研究[J]. 中国临床药理学与治疗学, 2017, 22(5): 560-564.
[14]	丛海涛，李中华，陈斌，丁进峰，王惠琴，陈玲阳. 右美托咪定对小鼠全身炎性细胞因子水平的作用及其机制研究[J]. 中国临床药理学与治疗学, 2017, 22(3): 260-266.
[15]	张佩红，陈啸洪，陈冰蓉，李华浚. 哮喘儿童血清细胞因子水平及布拉氏酵母菌干预的研究[J]. 中国临床药理学与治疗学, 2017, 22(3): 332-336.