白介素-10-627基因多态性和儿童哮喘的相关性研究
摘要
目的 细胞因子在哮喘发病机制中有很重要的作用，近年来人们发现某些细胞因子的遗传多态性与哮喘的发病存在一定的相关性。IL—10有广泛的免疫抑制和抗炎作用，是哮喘发病中的一种抗炎因子，其参与哮喘的发病机制基本得到肯定，但对于哮喘儿童，IL—10与遗传因素的作用目前还不清楚。 通过研究白介素—10(IL-10)基因—627位点多态性与儿童哮喘的相关性，探讨哮喘儿童的易感性。方法 选择中国昆明地区的汉族儿童为研究对象。实验对象分两组，病例组为50例确诊的支气管哮喘患儿，诊断标准采用《诸福堂实用儿科学》(第七版)：对照组为36名健康体检儿童。采用限制性内切酶Rsa Ⅰ，通过聚合酶链反应—限制性片段长度多态性(PCR—RFLP)分析、基因测序等技术测定IL-10—627位点多态性，比较两组儿童该位点的基因型和等位基因突变频率。数据用SPSS12.0计算机统计软件进行x~2检验。结果 哮喘组三种基因型CC、CA、从分别为12.0％、48.0％、40.0％；健康组三种基因型CC、CA、AA分别为8.3％、50.0％、41.7％。两组基因型分布频率差异无显著性(P＞0.05)。哮喘组C和A的等位基因分布频率分别为36.0％、64.0％；健康组C和A的等位基因分布频率分别为31.9％、68.1％。两组等位基因分布频率差异无显著性(P＞0.05)。基因测序证实IL-10—627 C→A是突变位点。结论 本次研究结果发现IL-10基因—627位点的基因型和等位基因在哮喘组与对照组间无差异，表明IL-10基因-627位点多态性可能与哮喘儿童易感性无关，可能与环境因素、种族等有关。
Objective Cytokines play a part role in the pathogenesis of asthma and recent studies found there are some associations between the pathogenesis of asthma and polymorphisms of several cytokines. Interleukin-10 is an antiinflammatory cytokine in asthma that plays a role in both immunoinhibition and antiinflammation. But the association between the polymorphism of IL-10 gene and hereditary susceptibility in children with asthma is unknown. In order to explore the hereditary susceptibility of children with asthma, we detect the association between the single nucleotide polymorphism (SNP) of IL-10 and childhood asthma to investigate susceptibility in children with asthma. Methods Subjects of Han ethnic were selected from Kunming City in China. The study was conducted in two different groups. 50 asthmatic children were
Objective Cytokines play a part role in the pathogenesis of asthma and recent studies found there are some associations between the pathogenesis of asthma and polymorphisms of several cytokines. Interleukin-10 is an antiinflammatory cytokine in asthma that plays a role in both immunoinhibition and antiinflammation. But the association between the polymorphism of IL-10 gene and hereditary susceptibility in children with asthma is unknown. In order to explore the hereditary susceptibility of children with asthma, we detect the association between the single nucleotide polymorphism (SNP) of IL-10 and childhood asthma to investigate susceptibility in children with asthma. Methods Subjects of Han ethnic were selected from Kunming City in China. The study was conducted in two different groups. 50 asthmatic children were
引文
1．尹晓娟，李为明．儿童哮喘遗传学进展(J)．中华儿科杂志，1999，37(12)：7707．
2. Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L. Interleukin-10 and transforming growth factor-[beta] promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med. 1998:158:1958-1962.
3. Karjalinen J, Hulkkonen J, Nieminen MM, et al. Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating immunoglobulin E in adult asthma. Clin Exp Allergy. 2003:33:78-83.
4．陈育智．支气管哮喘．诸福堂实用儿科学(第七版)，北京：人民卫生出版社，2002，631—642．
5. Hang LW, Hsia TC, Chen WC, et al. Interleukin-10 Gene-627 Allele Variants ,Not Interleukin-1 Beta Gene and Receptor Antagonist Gene Polymorphisms, Are Associated With Atopic Bronchial Asthma. Journal of Clinical Laboratory Analysis. 2003,17:168-173.
6．Volgel Motulsky．人类遗传学．罗会元，译．第三版．北京：人民卫生出版社，1999，749-750．
7. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 2005;5:271-283.
8. Takanashi S, Hasegawa Y, Kanehira Y, et al. Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers[J].Eur Respir J, 1999,14(2)309-314.
9. Roncarolo MG, Levings MK. The role of different subsets of T regulatory cells in controlling autoimmunity[J].Curr Opin Immunol, 2000,12(6):676-683.
10. Eskdale J, Gallagher G, Verweij CL, et al. Interleukin-10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acaol Sci USA, 1998,95:9465-9470.
11. Hsu DH, Dubbles CK. Expression of Interleukin-10 in BALF in patients with Asthma[J].J Allergy Clin Immunol, 1996, 97(6):1288—1296.
12. Borish L, Aarons A, Rumbyrt J, et al. Interleukin-10 regulation in normal subjects and patients with asthma[J].J Allergy Clin Immunol, 1996,97(6):1288-1296.
13. Gauvreau GM, Delex AK, Swwilson AC. Expression of Interleukin-10 in sputum patients with Asthma[J].Am J Respir Crit Care Med, 1999, 160(18):640—647.
14. John M, Lim S, Serbold J, et al. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1 alpha, granulocyte-macrophage colony-stimulating factor, and interferongamma release form alveolar macrophages in asthma[J].Am J Respir Crit Care Med, 1998,157(1):256-262.
15. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rational behind promoter-based candidate gene studies(IL-4 and IL-10)[J].Am J Respir Crit Care Med, 1997;156:S152-155.
16. Lim S, Crawley E, Woo P, et al. Haplotype associated with low interleukin-10 production in patients with severe asthma. 1998;Lancet 352:113.
17．张嘉琳，陈虹，胡良平等．白细胞介素4和10基因多态性与儿童哮喘的相关性及对细胞因子表达的影响．中华医学杂志，2002，82(2)：114-118．
18. Chatterjee R, Batra J, Kumar A, t al. Interleukin-10 promoter polymorphisms and atopic asthma in North Indians. Clin Exp Allergy. 2005,35(7):914-9.
19．张嘉琳．IL-4和IL-10基因启动子区多态性与哮喘．国外医学免疫学分册．2003，26(3)：104—107．
20. Lyon H, Lange C, Lake S, et al. IL-10 gene polymorphisms are associated with asthma phenotypes in children. Genet Epidemid. 2004,26(2):155-165.
1．尹晓娟，李为明．儿童哮喘遗传学进展(J)．中华儿科杂志，1999，37(12)：7707．
2. Lanny J, Rosenwasser,MD Denver. et al. Biologic activities of IL-1 and its role in human disease. J Allergy Clin Immunol, 1998;102:344-349.
3. Takanashi S, Hasegawa Y, Kanehira Y, et al. interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers[J].Eur Respir J, 1999,14(2):309-314.
4. John M, Lim S, Seybold J, et al. Inhaled eortieosteroids increase IL-10 but reduce maerophage inflammatory protein-1α ,granuloeyte-maerophage colony stimulating factor, and interferon-γ release from alveolar maerophages in asthma[J].Am J Respair Grit Care Med, 1998,157(1):256-262.
5．蒋东波，李华强，史源，等．哮喘患儿外周血白细胞介素10水平及其对白介素2等的调节作用[J]．中华儿科杂志，1993，37(1)：28-31．
6. Tillie-leblond I, Pugin J, Marquette CH, et al. Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmatics[J].Am J Respir Crit Care Med, 1999,159(2): 487-497.
7. Gohlke H, Illig T, Bahnweg M, et al. Association of the interleukin-1 receptor antagonist gene with asthma. Am J Respir Crit Care Med, 2004 1; 169(11): 1217-1223.
8. Dinarello. CA. Interleukin-1[J]. Cytokine Growth Factor Rev, 1997; 8.(4): 253-256.
9．徐峰．白介素—1参与支气管哮喘的相关机制．国外医学呼吸系统分册，2002，22(6)：297—299．
10. mao XQ, Kawar M, Yamashita T, et al. Imbalance Production between inteleukin-1β(IL-1β) and IL-1 Receptor Antagonist(IL-1Ra) in Bronchial Asthma. Biochem Biophysical Res Commun, 2000; 276:607-612.
11. Jedrzkiewicz S, Nakamura H, Silverman ES, et al. IL-1β induces eotaxin gene transcription in A549 airway epithelial eells through NF-κB. Am J. Physi, 2000; 279: L1058-1065.
12．李红霞，张进川．白介素-10对急性肺损伤的保护作用[J]．国外医学呼吸系统分册，2000，20(2)：94-96．
13. Reynolds AM, Holmes MD, Scicchitano R. Interleukin-1beta and tumour neceosis factor-alpha increase microvascular leakage in the guinea pig traohea. Respirology. 2002, 7(1):23-28.
14. De. Amici M, Puggioni P, Casali L, et al. Variations in serum levels of interleukin(IL)-1 beta, IL-2, IL-6, and tumor necrosis factor alpha during specific immunotherapy[J]. Ann Allergy Asthma Immunol, 2001, 86 (3): 311-313.
15, Lee KS, Jin SM, Kim HJ, et al. Matrix metallop rote inase inhibitor regulates inflammatory cell migration by toluene diisocyanate-induced asthma[J].J Allergy Clin Immunol, 2003,111(6):1278-1284.
16. Yang Y, Bin W, Aksoy MO, et al. Regulation of interkeukin-1 beta and interleukin-1 beta inhibitor release by human airway epithelial cells[J].Eur Respir J, 2004, 24(3):360-366.
17. Molimard M, Advenier C. Approach to bronchial hyperreactivity in vitro[J].Therapie 1999,54(1) :75-78.
18. Frossard N, Naline F, Olgart Hoglund C. et al. Nerve growth factor is released by IL-1beta and induces hyperresponsiveness of the human isolated bronchus. Eur Respir J. 2005 ,26(1):15-20.
19. Faffe DS, Flynt L, Mellema M, et al. Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-lbeta. Am J Physiol Lung Cell Mol Physiol, 2005 , 288(6):L1040-1048.
20. Martin, Christian, Wohlsen A, et al. Changes in airway resistance by simultaneous exposure to TNF-α and IL-1β in perfused rat lungs. Am J Physiol, 2001;280:L595-601.
21. Wuyts WA, Vanaudenaerde BM, Dupont LJ, et al. Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells. Respir Med, 2003 ,97(7):811-817.
22. Hallsworth MP, Twort C, Lee TH, et al. β2 — Adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells.Br J Pharmacol, 2001;132:729-741.
23. Amici D M, Puggioni F, Cssali L,et al. Variations in serum levels of nterleukin(IL)-lbeta, IL-2, IL-6,and tumor necrosis factor-alpha during specific immunotherapy[J]. Ann Allergy Asthma Immunol, 2001,86:311.
24. Ghaffar O, Hamid Q, Renzi PM, et al. Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth musle cells[J].Am J Respir Crit Care Med, 1999;159:1933-1942.
25.de Kluijver J, Grunberg K, Pons D. et al. Interleukin-1beta and interleukin-1ra levels in nasal lavages during experimental rhinovirus infection in asthmatic and non-asthmatic subjects Clin Exp Allergy, 2003, 33(10):1415-1418.
26. Amrol DJ, Hagaman DD, Sheller JR, et al. Soluble CD23 and interleukin-1 receptor antagonist in human asthmatics following antigen challenge. J Asthma, 2005 ,42(1):73-76.
27. Hawrylowicz CM, O' Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol ,2005;5:271-283.
28. Hsu DH, Dubbles CK. Expression of Interleukin-10 in BALF in patients with Asthma[J].J Allergy Clin Immunol, 1996, 97(6):1288-1296.
29. Gauvreau GM, Delex AK, Swwilson AC. Expression of Interleukin-10 in sputum patients with Asthma[J].Am J Respir Crit Care Med, 1999, 160(18): 640-647.
30. Oh JW, Seroogy CM, Meyer EH, et al.CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hypereactivity and inflammation[J].J Allergy Clin Immunol, 2002, 110(3):460-468.
31.Ameredes BT, Sethi JM, Liu HL. et al. Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10. Am J Physiol Lung Cell Mol Physiol, 2005 , 288(5):L868-873.
32. Stelmach I, Jetzynska J, Kuna P, et al. A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and beta-agonist treatment on IL-10 serum levels in children with asthma[J].Clin Exp Allergy, 2002, 32(2):264-269.
33. Stelmach I, Majak P, Jerzynska J, Kuna P. The effect of treatment with montelukast on in vitro interleukin-10 production of mononuclear cells of children with asthma. Clin Exp Allergy,2005;35(2):213-20.
1．王振华，赵凯姝，鲁继荣等．血小板活化因子乙酞水解酶基因多态性与儿童哮喘易感性关系的研究．中国实用儿科杂志，2004，19(3)：159-161．
2．中华医学会儿科学分会呼吸学组(2003年修订)．儿童支气管哮喘防治常规(试行)．中华儿科杂志，2004，42(2)：100-106．
3. Hang LW, Hsia TC, Chen WC, et al. Interleukin-10 Gene-627 Allele Variants ,Not Interleukin-1 Beta Gene and Receptor Antagonist Gene Polymorphism Are Associated With Atopic Bronchial Asthma. Journal of Clinical Laboratory Analysis. 2003,17:168-173.
4. Gohlke H, Illig T, Bahnweg M, et al. Association of the interleukin-1 receptor antagonist gene with asthma. Am J Respir Crit Care Med. 2004, 1;169(11):1217-1223.
5. Dinarello CA. Interleukin-l[J].Cytokine Growth Factor Rev, 1997; 8(4): 253-256.
6. De Amici M, Puggioni P, Casali L, et al. Variations in serum levels of interleukin(IL)-l beta, IL-2, IL-6, and tumor necrosis factor alpha during specific immunotherapy[J]. Ann Allergy Asthma Immunol, 2001,86(3):311-313.
7. Lee KS, Jin SM, Kim HJ, et al. Matrix metallop rote inase inhibitor regulates inflammatory cell migration by toluene diisocyanate-induced asthma[J].J Allergy Clin Immunol, 2003, 111(6):1278-1284.
8. Yang Y, Bin W, Aksoy MO, et al. Regulation of interkeukin-1 beta and interleukin-1 beta inhibitor release by human airway epithelial cells[J].Eur Respir J, 2004, 24(3):360-366.
9. Molimard M, Advenier C. Approach to bronchial hyperreactivity in vitro[J]. Therapie 1999, 54(1):75-78.
10. Karjalainen J, Nieminen MM, Aromaa A, et al. The IL-1 beta genotype carries asthma susceptibility only in men. J Allergy Clin Immunol. 2002 Mar;109(3):514-516.
2. Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L. Interleukin-10 and transforming growth factor-[beta] promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med. 1998:158:1958-1962.
3. Karjalinen J, Hulkkonen J, Nieminen MM, et al. Interleukin-10 gene promoter region polymorphism is associated with eosinophil count and circulating immunoglobulin E in adult asthma. Clin Exp Allergy. 2003:33:78-83.
4．陈育智．支气管哮喘．诸福堂实用儿科学(第七版)，北京：人民卫生出版社，2002，631—642．
5. Hang LW, Hsia TC, Chen WC, et al. Interleukin-10 Gene-627 Allele Variants ,Not Interleukin-1 Beta Gene and Receptor Antagonist Gene Polymorphisms, Are Associated With Atopic Bronchial Asthma. Journal of Clinical Laboratory Analysis. 2003,17:168-173.
6．Volgel Motulsky．人类遗传学．罗会元，译．第三版．北京：人民卫生出版社，1999，749-750．
7. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol 2005;5:271-283.
8. Takanashi S, Hasegawa Y, Kanehira Y, et al. Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers[J].Eur Respir J, 1999,14(2)309-314.
9. Roncarolo MG, Levings MK. The role of different subsets of T regulatory cells in controlling autoimmunity[J].Curr Opin Immunol, 2000,12(6):676-683.
10. Eskdale J, Gallagher G, Verweij CL, et al. Interleukin-10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acaol Sci USA, 1998,95:9465-9470.
11. Hsu DH, Dubbles CK. Expression of Interleukin-10 in BALF in patients with Asthma[J].J Allergy Clin Immunol, 1996, 97(6):1288—1296.
12. Borish L, Aarons A, Rumbyrt J, et al. Interleukin-10 regulation in normal subjects and patients with asthma[J].J Allergy Clin Immunol, 1996,97(6):1288-1296.
13. Gauvreau GM, Delex AK, Swwilson AC. Expression of Interleukin-10 in sputum patients with Asthma[J].Am J Respir Crit Care Med, 1999, 160(18):640—647.
14. John M, Lim S, Serbold J, et al. Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1 alpha, granulocyte-macrophage colony-stimulating factor, and interferongamma release form alveolar macrophages in asthma[J].Am J Respir Crit Care Med, 1998,157(1):256-262.
15. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: the rational behind promoter-based candidate gene studies(IL-4 and IL-10)[J].Am J Respir Crit Care Med, 1997;156:S152-155.
16. Lim S, Crawley E, Woo P, et al. Haplotype associated with low interleukin-10 production in patients with severe asthma. 1998;Lancet 352:113.
17．张嘉琳，陈虹，胡良平等．白细胞介素4和10基因多态性与儿童哮喘的相关性及对细胞因子表达的影响．中华医学杂志，2002，82(2)：114-118．
18. Chatterjee R, Batra J, Kumar A, t al. Interleukin-10 promoter polymorphisms and atopic asthma in North Indians. Clin Exp Allergy. 2005,35(7):914-9.
19．张嘉琳．IL-4和IL-10基因启动子区多态性与哮喘．国外医学免疫学分册．2003，26(3)：104—107．
20. Lyon H, Lange C, Lake S, et al. IL-10 gene polymorphisms are associated with asthma phenotypes in children. Genet Epidemid. 2004,26(2):155-165.
1．尹晓娟，李为明．儿童哮喘遗传学进展(J)．中华儿科杂志，1999，37(12)：7707．
2. Lanny J, Rosenwasser,MD Denver. et al. Biologic activities of IL-1 and its role in human disease. J Allergy Clin Immunol, 1998;102:344-349.
3. Takanashi S, Hasegawa Y, Kanehira Y, et al. interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers[J].Eur Respir J, 1999,14(2):309-314.
4. John M, Lim S, Seybold J, et al. Inhaled eortieosteroids increase IL-10 but reduce maerophage inflammatory protein-1α ,granuloeyte-maerophage colony stimulating factor, and interferon-γ release from alveolar maerophages in asthma[J].Am J Respair Grit Care Med, 1998,157(1):256-262.
5．蒋东波，李华强，史源，等．哮喘患儿外周血白细胞介素10水平及其对白介素2等的调节作用[J]．中华儿科杂志，1993，37(1)：28-31．
6. Tillie-leblond I, Pugin J, Marquette CH, et al. Balance between proinflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmatics[J].Am J Respir Crit Care Med, 1999,159(2): 487-497.
7. Gohlke H, Illig T, Bahnweg M, et al. Association of the interleukin-1 receptor antagonist gene with asthma. Am J Respir Crit Care Med, 2004 1; 169(11): 1217-1223.
8. Dinarello. CA. Interleukin-1[J]. Cytokine Growth Factor Rev, 1997; 8.(4): 253-256.
9．徐峰．白介素—1参与支气管哮喘的相关机制．国外医学呼吸系统分册，2002，22(6)：297—299．
10. mao XQ, Kawar M, Yamashita T, et al. Imbalance Production between inteleukin-1β(IL-1β) and IL-1 Receptor Antagonist(IL-1Ra) in Bronchial Asthma. Biochem Biophysical Res Commun, 2000; 276:607-612.
11. Jedrzkiewicz S, Nakamura H, Silverman ES, et al. IL-1β induces eotaxin gene transcription in A549 airway epithelial eells through NF-κB. Am J. Physi, 2000; 279: L1058-1065.
12．李红霞，张进川．白介素-10对急性肺损伤的保护作用[J]．国外医学呼吸系统分册，2000，20(2)：94-96．
13. Reynolds AM, Holmes MD, Scicchitano R. Interleukin-1beta and tumour neceosis factor-alpha increase microvascular leakage in the guinea pig traohea. Respirology. 2002, 7(1):23-28.
14. De. Amici M, Puggioni P, Casali L, et al. Variations in serum levels of interleukin(IL)-1 beta, IL-2, IL-6, and tumor necrosis factor alpha during specific immunotherapy[J]. Ann Allergy Asthma Immunol, 2001, 86 (3): 311-313.
15, Lee KS, Jin SM, Kim HJ, et al. Matrix metallop rote inase inhibitor regulates inflammatory cell migration by toluene diisocyanate-induced asthma[J].J Allergy Clin Immunol, 2003,111(6):1278-1284.
16. Yang Y, Bin W, Aksoy MO, et al. Regulation of interkeukin-1 beta and interleukin-1 beta inhibitor release by human airway epithelial cells[J].Eur Respir J, 2004, 24(3):360-366.
17. Molimard M, Advenier C. Approach to bronchial hyperreactivity in vitro[J].Therapie 1999,54(1) :75-78.
18. Frossard N, Naline F, Olgart Hoglund C. et al. Nerve growth factor is released by IL-1beta and induces hyperresponsiveness of the human isolated bronchus. Eur Respir J. 2005 ,26(1):15-20.
19. Faffe DS, Flynt L, Mellema M, et al. Oncostatin M causes VEGF release from human airway smooth muscle: synergy with IL-lbeta. Am J Physiol Lung Cell Mol Physiol, 2005 , 288(6):L1040-1048.
20. Martin, Christian, Wohlsen A, et al. Changes in airway resistance by simultaneous exposure to TNF-α and IL-1β in perfused rat lungs. Am J Physiol, 2001;280:L595-601.
21. Wuyts WA, Vanaudenaerde BM, Dupont LJ, et al. Involvement of p38 MAPK, JNK, p42/p44 ERK and NF-kappaB in IL-1beta-induced chemokine release in human airway smooth muscle cells. Respir Med, 2003 ,97(7):811-817.
22. Hallsworth MP, Twort C, Lee TH, et al. β2 — Adrenoceptor agonists inhibit release of eosinophil-activating cytokines from human airway smooth muscle cells.Br J Pharmacol, 2001;132:729-741.
23. Amici D M, Puggioni F, Cssali L,et al. Variations in serum levels of nterleukin(IL)-lbeta, IL-2, IL-6,and tumor necrosis factor-alpha during specific immunotherapy[J]. Ann Allergy Asthma Immunol, 2001,86:311.
24. Ghaffar O, Hamid Q, Renzi PM, et al. Constitutive and cytokine-stimulated expression of eotaxin by human airway smooth musle cells[J].Am J Respir Crit Care Med, 1999;159:1933-1942.
25.de Kluijver J, Grunberg K, Pons D. et al. Interleukin-1beta and interleukin-1ra levels in nasal lavages during experimental rhinovirus infection in asthmatic and non-asthmatic subjects Clin Exp Allergy, 2003, 33(10):1415-1418.
26. Amrol DJ, Hagaman DD, Sheller JR, et al. Soluble CD23 and interleukin-1 receptor antagonist in human asthmatics following antigen challenge. J Asthma, 2005 ,42(1):73-76.
27. Hawrylowicz CM, O' Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma. Nat Rev Immunol ,2005;5:271-283.
28. Hsu DH, Dubbles CK. Expression of Interleukin-10 in BALF in patients with Asthma[J].J Allergy Clin Immunol, 1996, 97(6):1288-1296.
29. Gauvreau GM, Delex AK, Swwilson AC. Expression of Interleukin-10 in sputum patients with Asthma[J].Am J Respir Crit Care Med, 1999, 160(18): 640-647.
30. Oh JW, Seroogy CM, Meyer EH, et al.CD4 T-helper cells engineered to produce IL-10 prevent allergen-induced airway hypereactivity and inflammation[J].J Allergy Clin Immunol, 2002, 110(3):460-468.
31.Ameredes BT, Sethi JM, Liu HL. et al. Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10. Am J Physiol Lung Cell Mol Physiol, 2005 , 288(5):L868-873.
32. Stelmach I, Jetzynska J, Kuna P, et al. A randomized, double-blind trial of the effect of glucocorticoid, antileukotriene and beta-agonist treatment on IL-10 serum levels in children with asthma[J].Clin Exp Allergy, 2002, 32(2):264-269.
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