• 1 重慶醫(yī)科大學(xué)附屬第一醫(yī)院第一分院急診科（重慶，400015）;2 重慶市第六人民醫(yī)院內(nèi)科;

【摘要】　 支氣管哮喘是一種由多種細(xì)胞包括氣道的炎性細(xì)胞、結(jié)構(gòu)細(xì)胞和細(xì)胞組分參與的氣道慢性炎癥性疾病。臨床上少數(shù)患者通過充分的哮喘治療包括使用全身性激素治療后仍不能有效控制， 通常稱為“難治性哮喘”。免疫反應(yīng)在難治性哮喘發(fā)病機(jī)制中起重要作用，而Th1/Th2失衡貫穿于難治性哮喘發(fā)病的整個過程?，F(xiàn)就難治性哮喘中Th1/Th2失衡機(jī)制，以及影響因子（干擾素-γ、白介素-12、白介素-4、白介素-17，白介素-33和轉(zhuǎn)化生長因子-β等）的研究作一綜述，以深入探討難治性哮喘的發(fā)病機(jī)制。

引用本文： 胡鑫,沈唯薇. 難治性哮喘中Th1/Th2失衡機(jī)制. 華西醫(yī)學(xué), 2011, 26(9): 1428-1431. doi: 復(fù)制

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2. 　Redington AE, Howarth PH. Airway wall remodelling in asthma[J]. Thorax, 1997, 52(4): 310-312.
3. 　Del Prete G, Maggi E, Romagnani S. Human Th1 and Th2 cells: functional properties, mechanisms of regulation,and role in disease[J]. Lab Invest, 1994, 70(3): 299-306.
4. 　Piccinni MP, Giudizi MG, Biagiotti R, et al. Progesterone favorsthe development of human T helper cells producing Th2-type cytokines and promots both IL-4 production and membrane CD30 expression in established Th1 cell clones[J]. J Immunol, 1995, 155(1): 128-133.
5. 　Blink SE, Fu YX. IgE regulates T helper cell differentiation through FcgammaRIII mediated dendritic cell cytokine modulation[J]. Cell Immunol, 2010, 264(1): 54-60.
6. 　Varga EM, Wachholz P, Nouri-Aria KT, et al. T cells from human allergen-induced late asthmatic responses express IL-12 receptor beta 2 subunit mRNA and respond to IL-12 in vitro[J]. J Immunol, 2000, 165(5): 2877-2885.
7. 　Choi IS, Cui Y, Koh YA, et al. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics[J]. Korean J Intern Med, 2008, 23(4): 176-181.
8. 　Hamid QA, Minshall EM. Molecular pathyology of allergic disease[J]. J Allergy Clin Immunol, 2000, 105(1): 20-36.
9. 　Deo SS, Mistry KJ, Kakade AM, et al. Role played by Th2 type cytokines in IgE mediated allergy and asthma[J]. Lung India, 2010, 27(2): 66-71.
10. 　Xu Q, Leung DY, Kisich KO. Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mrna to glucocorticoid receptor in neutrophils[J]. J Biol Chem, 2000, 278(29): 27112-27118.
11. 　Cosmi L, Liotta F, Maggi E, et al. Th17 cell: new players in asthma pathogenesis[J]. J Allergy Clin Immunol, 2011, 66(8): 989-98.
12. 　Al-Ramli W, Prefontaine D, Chouiali F, et al. T(H) 17-associated cytokinase (IL-17A and IL-17F) in severe asthma[J]. J Allergy Clin Immunol, 2009, 123(5): 1185-1187.
13. 　Zhao Y, Yang J, Gao YD, et al. Th17 immunity in patients with allergic asthma[J]. Int Arch Allergy Immunol, 2010, 151(4): 297-307.
14. 　Rook W. TGF-β1 paradox in asthma[J].　Trends Immunol, 2001, 22(6): 299.
15. 　Minshall EM, Leung NYM, Martin RJ, et al. Eosinophil-assiociated TGF-β1 mRNA expression and airwalls fibrosis in bronchial asthma[J]. Am J Respire Cell Mol Biol, 1997, 17(3):326-333.
16. 　Mak JC, Rousell J, Haddad EB, et al. Transforming growth factor-beta1 inhibits beta2-adrenoceptor gene transcription[J]. Naunyn Schmiedebergs Arch Pharmacol, 2000, 362(6): 520-525.
17. 　Préfontaine D, Lajoie-kadoch S, Foley S, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cell[J]. J Immunol, 2009, 183(8): 5094-5103.
18. 　Wegmann M. Th2 cells as targets for therapeutic intervention in allergic bronchial asthma[J]. Expert Rev Mol Diagn, 2009, 9(1): 85-100.
19. 　Hartl D, Koller B, Mehlhon AT, et al. Quantitative and functional impairment of pulmonary CD4+ CD25hi regulatory T cells in pediatric asthma[J].J Allergy Clin Immunol, 2007, 119(5): 1258-1266.
20. 　符州, 楊錫強(qiáng), 李成榮. 甲基強(qiáng)的松龍對哮喘患兒PBMC分泌TH源性細(xì)胞因子的影響作用研究[J]. 中華微生物學(xué)和免疫學(xué)雜志, 2000, 20(6): 548.
21. 　Randolph DA, Stephens R, Carruthers CJ, et al. Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation[J].J Clin Invest, 1999, 104(8): 1021-1029.
  1. 1. 　陳灝珠. 實(shí)用內(nèi)科學(xué)[M]. 10版. 北京: 人民衛(wèi)生出版社, 1999: 1379-1398.
  2. 2. 　Redington AE, Howarth PH. Airway wall remodelling in asthma[J]. Thorax, 1997, 52(4): 310-312.
  3. 3. 　Del Prete G, Maggi E, Romagnani S. Human Th1 and Th2 cells: functional properties, mechanisms of regulation,and role in disease[J]. Lab Invest, 1994, 70(3): 299-306.
  4. 4. 　Piccinni MP, Giudizi MG, Biagiotti R, et al. Progesterone favorsthe development of human T helper cells producing Th2-type cytokines and promots both IL-4 production and membrane CD30 expression in established Th1 cell clones[J]. J Immunol, 1995, 155(1): 128-133.
  5. 5. 　Blink SE, Fu YX. IgE regulates T helper cell differentiation through FcgammaRIII mediated dendritic cell cytokine modulation[J]. Cell Immunol, 2010, 264(1): 54-60.
  6. 6. 　Varga EM, Wachholz P, Nouri-Aria KT, et al. T cells from human allergen-induced late asthmatic responses express IL-12 receptor beta 2 subunit mRNA and respond to IL-12 in vitro[J]. J Immunol, 2000, 165(5): 2877-2885.
  7. 7. 　Choi IS, Cui Y, Koh YA, et al. Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics[J]. Korean J Intern Med, 2008, 23(4): 176-181.
  8. 8. 　Hamid QA, Minshall EM. Molecular pathyology of allergic disease[J]. J Allergy Clin Immunol, 2000, 105(1): 20-36.
  9. 9. 　Deo SS, Mistry KJ, Kakade AM, et al. Role played by Th2 type cytokines in IgE mediated allergy and asthma[J]. Lung India, 2010, 27(2): 66-71.
  10. 10. 　Xu Q, Leung DY, Kisich KO. Serine-arginine-rich protein p30 directs alternative splicing of glucocorticoid receptor pre-mrna to glucocorticoid receptor in neutrophils[J]. J Biol Chem, 2000, 278(29): 27112-27118.
  11. 11. 　Cosmi L, Liotta F, Maggi E, et al. Th17 cell: new players in asthma pathogenesis[J]. J Allergy Clin Immunol, 2011, 66(8): 989-98.
  12. 12. 　Al-Ramli W, Prefontaine D, Chouiali F, et al. T(H) 17-associated cytokinase (IL-17A and IL-17F) in severe asthma[J]. J Allergy Clin Immunol, 2009, 123(5): 1185-1187.
  13. 13. 　Zhao Y, Yang J, Gao YD, et al. Th17 immunity in patients with allergic asthma[J]. Int Arch Allergy Immunol, 2010, 151(4): 297-307.
  14. 14. 　Rook W. TGF-β1 paradox in asthma[J].　Trends Immunol, 2001, 22(6): 299.
  15. 15. 　Minshall EM, Leung NYM, Martin RJ, et al. Eosinophil-assiociated TGF-β1 mRNA expression and airwalls fibrosis in bronchial asthma[J]. Am J Respire Cell Mol Biol, 1997, 17(3):326-333.
  16. 16. 　Mak JC, Rousell J, Haddad EB, et al. Transforming growth factor-beta1 inhibits beta2-adrenoceptor gene transcription[J]. Naunyn Schmiedebergs Arch Pharmacol, 2000, 362(6): 520-525.
  17. 17. 　Préfontaine D, Lajoie-kadoch S, Foley S, et al. Increased expression of IL-33 in severe asthma: evidence of expression by airway smooth muscle cell[J]. J Immunol, 2009, 183(8): 5094-5103.
  18. 18. 　Wegmann M. Th2 cells as targets for therapeutic intervention in allergic bronchial asthma[J]. Expert Rev Mol Diagn, 2009, 9(1): 85-100.
  19. 19. 　Hartl D, Koller B, Mehlhon AT, et al. Quantitative and functional impairment of pulmonary CD4+ CD25hi regulatory T cells in pediatric asthma[J].J Allergy Clin Immunol, 2007, 119(5): 1258-1266.
  20. 20. 　符州, 楊錫強(qiáng), 李成榮. 甲基強(qiáng)的松龍對哮喘患兒PBMC分泌TH源性細(xì)胞因子的影響作用研究[J]. 中華微生物學(xué)和免疫學(xué)雜志, 2000, 20(6): 548.
  21. 21. 　Randolph DA, Stephens R, Carruthers CJ, et al. Cooperation between Th1 and Th2 cells in a murine model of eosinophilic airway inflammation[J].J Clin Invest, 1999, 104(8): 1021-1029.