• 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(guò)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(chēng)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(gè)過(guò)程。現(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(zhǎng)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(duì)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(duì)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.